An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
Lack of stability of a joint or joint prosthesis. Factors involved are intra-articular disease and integrity of extra-articular structures such as joint capsule, ligaments, and muscles.
The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).
Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
Mapping of the KARYOTYPE of a cell.
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004)
A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
A chromosome instability syndrome resulting from a defective response to DNA double-strand breaks. In addition to characteristic FACIES and MICROCEPHALY, patients have a range of findings including RADIOSENSITIVITY, immunodeficiency, increased cancer risk, and growth retardation. Causative mutations occur in the NBS1 gene, located on human chromosome 8q21. NBS1 codes for nibrin, the key regulator protein of the R/M/N (RAD50/MRE11/NBS1) protein complex which senses and mediates cellular response to DNA DAMAGE caused by IONIZING RADIATION.
The degree of replication of the chromosome set in the karyotype.
The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION.
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
An autosomal recessive disorder characterized by telangiectatic ERYTHEMA of the face, photosensitivity, DWARFISM and other abnormalities, and a predisposition toward developing cancer. The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase.
Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.
An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in BLOOM SYNDROME.
Defective nuclei produced during the TELOPHASE of MITOSIS or MEIOSIS by lagging CHROMOSOMES or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
DNA present in neoplastic tissue.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Specific loci that show up during KARYOTYPING as a gap (an uncondensed stretch in closer views) on a CHROMATID arm after culturing cells under specific conditions. These sites are associated with an increase in CHROMOSOME FRAGILITY. They are classified as common or rare, and by the specific culture conditions under which they develop. Fragile site loci are named by the letters "FRA" followed by a designation for the specific chromosome, and a letter which refers to which fragile site of that chromosome (e.g. FRAXA refers to fragile site A on the X chromosome. It is a rare, folic acid-sensitive fragile site associated with FRAGILE X SYNDROME.)
Mad2 is a component of the spindle-assembly checkpoint apparatus. It binds to and inhibits the Cdc20 activator subunit of the anaphase-promoting complex, preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Mad2 is required for proper microtubule capture at KINETOCHORES.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.
An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).
An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The simultaneous identification of all chromosomes from a cell by fluorescence in situ hybridization (IN SITU HYBRIDIZATION, FLUORESCENCE) with chromosome-specific florescent probes that are discerned by their different emission spectra.
Examination of CHROMOSOMES to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, KARYOTYPING is performed and/or the specific chromosomes are analyzed.
A Fanconi anemia complementation group protein that undergoes PHOSPHORYLATION by CDC2 PROTEIN KINASE during MITOSIS. It forms a complex with other FANCONI ANEMIA PROTEINS and helps protect CELLS from DNA DAMAGE by genotoxic agents.
The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.
The loss of some TELOMERE sequence during DNA REPLICATION of the first several base pairs of a linear DNA molecule; or from DNA DAMAGE. Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS.) Telomere shortening is involved in the progression of CELL AGING.
A diverse group of proteins whose genetic MUTATIONS have been associated with the chromosomal instability syndrome FANCONI ANEMIA. Many of these proteins play important roles in protecting CELLS against OXIDATIVE STRESS.
Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)
A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.
The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.
Induction and quantitative measurement of chromosomal damage leading to the formation of micronuclei (MICRONUCLEI, CHROMOSOME-DEFECTIVE) in cells which have been exposed to genotoxic agents or IONIZING RADIATION.
A cell line derived from cultured tumor cells.
Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.
The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.
A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.
A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)
The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
A method for comparing two sets of chromosomal DNA by analyzing differences in the copy number and location of specific sequences. It is used to look for large sequence changes such as deletions, duplications, amplifications, or translocations.
A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.
A Fanconi anemia complementation group protein that regulates the activities of CYTOCHROME P450 REDUCTASE and GLUTATHIONE S-TRANSFERASE. It is found predominately in the CYTOPLASM, but moves to the CELL NUCLEUS in response to FANCE PROTEIN.
A Fanconi anemia complementation group protein that is the most commonly mutated protein in FANCONI ANEMIA. It undergoes PHOSPHORYLATION by PROTEIN KINASE B and forms a complex with FANCC PROTEIN in the CELL NUCLEUS.
An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Established cell cultures that have the potential to propagate indefinitely.
Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard X-rays are the higher energy, shorter wavelength X-rays. Soft x-rays or Grenz rays are less energetic and longer in wavelength. The short wavelength end of the X-ray spectrum overlaps the GAMMA RAYS wavelength range. The distinction between gamma rays and X-rays is based on their radiation source.
The process by which the CYTOPLASM of a cell is divided.
The process by which a DNA molecule is duplicated.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.
An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or 6-mercaptopurine to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8.
A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.
A Fanconi anemia complementation group protein. It is an essential component of a nuclear core complex that protects the GENOME against CHROMOSOMAL INSTABILITY. It interacts directly with FANCG PROTEIN and helps stabilize a complex with FANCA PROTEIN and FANCC PROTEIN.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
A situation where one member (allele) of a gene pair is lost (LOSS OF HETEROZYGOSITY) or amplified.
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)
A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
Pathological processes of the OVARIES or the TESTES.
The presence of four sets of chromosomes. It is associated with ABNORMALITIES, MULTIPLE; and MISCARRAGES.
Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.
Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
The result of a positive or negative response (to drugs, for example) in one cell being passed onto other cells via the GAP JUNCTIONS or the intracellular milieu.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
The 46,XX gonadal dysgenesis may be sporadic or familial. Familial XX gonadal dysgenesis is transmitted as an autosomal recessive trait and its locus was mapped to chromosome 2. Mutation in the gene for the FSH receptor (RECEPTORS, FSH) was detected. Sporadic XX gonadal dysgenesis is heterogeneous and has been associated with trisomy-13 and trisomy-18. These phenotypic females are characterized by a normal stature, sexual infantilism, bilateral streak gonads, amenorrhea, elevated plasma LUTEINIZING HORMONE and FSH concentration.
The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single ZYGOTE, as opposed to CHIMERISM in which the different cell populations are derived from more than one zygote.
The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)
A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Immunologically detectable substances found in the CELL NUCLEUS.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION.
Tumors or cancer of the COLON.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the CELL CYCLE. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 2 in that it contains acidic N-terminal amino acid residues.
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).
Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)
Actual loss of portion of a chromosome.
A Fanconi anemia complementation group protein that undergoes mono-ubiquitination by FANCL PROTEIN in response to DNA DAMAGE. Also, in response to IONIZING RADIATION it can undergo PHOSPHORYLATION by ataxia telangiectasia mutated protein. Modified FANCD2 interacts with BRCA2 PROTEIN in a stable complex with CHROMATIN, and it is involved in DNA REPAIR by homologous RECOMBINATION.
Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.
MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.
A characteristic symptom complex.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Securin is involved in the control of the metaphase-anaphase transition during MITOSIS. It promotes the onset of anaphase by blocking SEPARASE function and preventing proteolysis of cohesin and separation of sister CHROMATIDS. Overexpression of securin is associated with NEOPLASTIC CELL TRANSFORMATION and tumor formation.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Tumors or cancer of the human BREAST.
An expression of the number of mitoses found in a stated number of cells.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
A region of DNA that is highly polymorphic and is prone to strand breaks, rearrangements or other MUTATIONS because of the nature of its sequence. These regions often harbor palindromic, or repetitive sequences (REPETITIVE SEQUENCES, NUCLEIC ACID). Variability in stability of the DNA sequence is seen at CHROMOSOME FRAGILE SITES.
A negative regulator of beta-catenin signaling which is mutant in ADENOMATOUS POLYPOSIS COLI and GARDNER SYNDROME.
Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
Biochemical identification of mutational changes in a nucleotide sequence.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A benign epithelial tumor with a glandular organization.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A species of POLYOMAVIRUS, originally isolated from the brain of a patient with progressive multifocal leukoencephalopathy. The patient's initials J.C. gave the virus its name. Infection is not accompanied by any apparent illness but serious demyelinating disease can appear later, probably following reactivation of latent virus.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with familial adenomatous polyposis (ADENOMATOUS POLYPOSIS COLI) and GARDNER SYNDROME, as well as some sporadic colorectal cancers.
A malignant epithelial tumor with a glandular organization.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Genes whose abnormal expression, or MUTATION are associated with the development, growth, or progression of NEOPLASMS.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Elements of limited time intervals, contributing to particular results or situations.
The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).
A general term for various neoplastic diseases of the lymphoid tissue.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.

Multiplex single-tube screening for mutations in the Nijmegen Breakage Syndrome (NBS1) gene in Hodgkin's and non-Hodgkin's lymphoma patients of Slavic origin. (1/873)

Patients with Nijmegen Breakage Syndrome (NBS) have a high risk to develop malignant diseases, most frequently B-cell lymphomas. It has been demonstrated that this chromosomal breakage syndrome results from mutations in the NBS1 gene that cause either a loss of full-length protein expression or expression of a variant protein. A large proportion of the known NBS patients are of Slavic origin who carry a major founder mutation 657del5 in exon 6 of the NBS1 gene. The prevalence of this mutation in Slav populations is reported to be high, possibly contributing to higher cancer risk in these populations. Therefore, if mutations in NBS1 are associated with higher risk of developing lymphoid cancers it would be most likely to be observed in these populations. A multiplex assay for four of the most frequent NBS1 mutations was designed and a series of 119 lymphoma patients from Slavic origin as well as 177 healthy controls were tested. One of the patients was a heterozygote carrier of the ACAAA deletion mutation in exon 6 (1/119). No mutation was observed in the control group, despite the reported high frequency (1/177). The power of this study was 30% to detect a relative risk of 2.0.  (+info)

Lymphoma development in Bax transgenic mice is inhibited by Bcl-2 and associated with chromosomal instability. (2/873)

Bax is a Bcl-2 family member that promotes apoptosis but has paradoxical effects on lymphoma development in p53-deficient mice. To better understand the mechanism of Bax-induced lymphoma development, the effect of Bax levels, p53 status and Bcl-2 coexpression on lymphoma development were determined. In addition, DNA content and cytogenetics were performed on young (premalignant) Lck-Bax mice as measures of genetic instability. Bax promoted lymphoma development in p53-deficient mice in a dose-dependent manner. Bax expression also led to lymphoma development in both p53 +/- and +/+ animals. Ploidy analysis in mice prior to the onset of overt thymic lymphomas demonstrated that Lck-Bax transgenic mice were more likely to be aneuploid and demonstrate increased chromosome instability. With tumor progression, aneuploidy increased and Bax expression was maintained. Importantly, coexpression of Bcl-2 delayed lymphoma development in Lck-Bax transgenic mice. These data support a model in which increased sensitivity to apoptosis leads directly to chromosome instability in developing T cells and may explain a number of paradoxical observations regarding Bcl-2 family members and the regulation of cancer.  (+info)

Chromosomal instability detected by fluorescence in situ hybridization in surgical specimens of non-small cell lung cancer is associated with poor survival. (3/873)

PURPOSE: Chromosomal instability (CIN) in non-small cell lung cancer (NSCLC) has yet to be well studied. We examined the relationship between CIN detected by fluorescence in situ hybridization and survival in patients with NSCLC. EXPERIMENTAL DESIGN: Touch preparations from 50 surgical specimens of NSCLC were studied. Tumors included 34 adenocarcinomas, 15 squamous cell carcinomas, and 1 large cell carcinoma. The pathologic stage was IA in 14, IB in 17, IIB in 8, IIIA in 9, and IIIB in 2 cases. Enumeration of chromosomes 3, 10, 11, and 17 was used to determine which tumors carried CIN. The association between CIN and survival was also analyzed. RESULTS: Disomy was most common, but tetrasomy and trisomy of the examined chromosomes were seen frequently. Fourteen tumors (28%) showed heterogeneity of all four chromosomes examined and were judged to be carrying CIN. Both univariate and multivariate analyses revealed that two factors, lymph node metastasis and CIN, were significant poor prognostic factors. CONCLUSIONS: CIN in NSCLC detected by fluorescence in situ hybridization is an independent factor predicting a poor prognosis.  (+info)

Chromosomal instability rather than p53 mutation is associated with response to neoadjuvant cisplatin-based chemotherapy in gastric carcinoma. (4/873)

PURPOSE: The objective of the study was to evaluate microsatellite alterations [microsatellite instability (MSI) and loss of heterozygosity (LOH)] and mutation in the p53 gene in relation to response and patient survival to a cisplatin-based neoadjuvant chemotherapy in gastric cancer. EXPERIMENTAL DESIGN: Fifty-three pretherapeutic gastric carcinoma biopsies were analyzed with 11 microsatellite markers. The entire coding region of the p53 gene (exons 2-11) was analyzed for mutations by denaturing high-pressure liquid chromatography and sequencing. p53 protein expression was evaluated by immunohistochemistry. Patients were treated with a cisplatin-based, neoadjuvant chemotherapy regimen. Therapy response was evaluated by computed tomography scan, endoscopy, and endoluminal ultrasound. The median follow-up of the patients was 45.6 months. RESULTS: p53 mutations were identified in 19 of the 53 (36%) analyzed tumors. No significant association with response or survival was found for p53 mutation or for p53 protein expression. MSI (either high-grade MSI or low-grade MSI) did not show a correlation with response. With respect to LOH, LOH at chromosome 17p13 showed a significant association with therapy response (P = 0.022) but did not reach statistical significance in terms of patient survival. The global LOH rate, expressed as fractional allelic loss (FAL), was assessed, and tumors were classified into tumors with a high (>0.5), medium (>0.25-0.5), and low (0-0.25) FAL value. A statistically significant association of FAL with therapy response was found (P = 0.003), with a high FAL being related to therapy response. The sensitivity, specificity, positive predictive value, and negative predictive value for FAL > 0.5 were 45%, 93%, 82%, and 72%, respectively. CONCLUSIONS: A high level of chromosomal instability (high FAL value) defines a subset of patients who are more likely to benefit from cisplatin-based neoadjuvant chemotherapy. p53 mutation status is not significantly associated with therapy response and is not a useful marker for response prediction.  (+info)

Drosophila melanogaster and D. simulans rescue strains produce fit offspring, despite divergent centromere-specific histone alleles. (5/873)

The interaction between rapidly evolving centromere sequences and conserved kinetochore machinery appears to be mediated by centromere-binding proteins. A recent theory proposes that the independent evolution of centromere-binding proteins in isolated populations may be a universal cause of speciation among eukaryotes. In Drosophila the centromere-specific histone, Cid (centromere identifier), shows extensive sequence divergence between D. melanogaster and the D. simulans clade, indicating that centromere machinery incompatibilities may indeed be involved in reproductive isolation and speciation. However, it is presently unclear whether the adaptive evolution of Cid was a cause of the divergence between these species, or merely a product of postspeciation adaptation in the separate lineages. Furthermore, the extent to which divergent centromere identifier proteins provide a barrier to reproduction remains unknown. Interestingly, a small number of rescue lines from both D. melanogaster and D. simulans can restore hybrid fitness. Through comparisons of cid sequence between nonrescue and rescue strains, we show that cid is not involved in restoring hybrid viability or female fertility. Further, we demonstrate that divergent cid alleles are not sufficient to cause inviability or female sterility in hybrid crosses. Our data do not dispute the rapid divergence of cid or the coevolution of centromeric components in Drosophila; however, they do suggest that cid underwent adaptive evolution after D. melanogaster and D. simulans diverged and, consequently, is not a speciation gene.  (+info)

The Fanconi Anemia/BRCA signaling pathway: disruption in cisplatin-sensitive ovarian cancers. (6/873)

Ovarian tumors often exhibit chromosome instability and hypersensitivity to the chemotherapeutic agent cisplatin. Recently, we have shown that this cellular phenotype may result from an acquired disruption of the Fanconi Anemia/BRCA (FA/BRCA) signaling pathway. Disruption results from methylation and silencing of one of the FA genes (FANCF), leading to cisplatin sensitivity. Restoration of this pathway is associated with demethylation of FANCF, leading to acquired cisplatinum resistance. The serial inactivation and reactivation of the FA/BRCA pathway has important implications for the diagnosis and treatment of ovarian cancers and related cancers.  (+info)

Long-term global gene expression patterns in irradiated human lymphocytes. (7/873)

Radiation-induced chromosomal instability has many features in common with genomic instability of cancer cells. In order to understand the delayed cellular response to ionizing radiation we have studied variations in the patterns of gene expression in primary human lymphocytes at various time points after gamma irradiation in vitro. Cells either exposed to 3 Gy of gamma rays in vitro or unexposed were subjected to long-term growth in bulk culture or as individual T-cell clones. Samples were taken at days 7, 17 or 55 from bulk cultures. The T-cell clones were harvested after 22-46 days. Total RNA was used to generate cDNA probes for hybridization to oligonucleotide arrays containing 12,625 gene templates (Affymetrix). The results showed that: (i) irradiation as well as culture time influence the gene expression patterns, (ii) the number of genes with increased or decreased expression in irradiated cells increases dramatically with increasing culture time, (iii) the changes of gene expression showed a significantly more diversified pattern in the irradiated T-cell clones than in non-irradiated clones. We conclude that the diversification of the transcriptome associated with radiation exposure reflects subtle changes of expression in many genes, rather than being the result of major changes in a few genes. Finally, (iv) we sorted out a set of genes whose change of expression correlates with radiation exposure in both bulk cultures and T-cell clones. Very few of these genes overlap with genes that change during the acute response to radiation. This set of genes may be regarded as a starting point for further studies of the cellular phenotype associated with radiation-induced genomic instability.  (+info)

Regional differences of somatic CAG repeat instability do not account for selective neuronal vulnerability in a knock-in mouse model of SCA1. (8/873)

Expression of unstable translated CAG repeats is the mutational mechanism in nine different neurodegenerative disorders. Although the products of genes harboring these repeats are widely expressed, a subset of neurons is vulnerable in each disease accounting for the different phenotypes. Somatic instability of the expanded CAG repeat has been implicated as a factor mediating the selective striatal neurodegeneration in Huntington disease. It remains unknown, however, whether such a mechanism contributes to the selective neurodegeneration in other polyglutamine diseases or not. To address this question, we investigated the pattern of CAG repeat instability in a knock-in mouse model of spinocerebellar ataxia type 1 (SCA1). Small pool PCR analysis on DNA from various neuronal and non-neuronal tissues revealed that somatic repeat instability was most remarkable in the striatum. In the two vulnerable tissues, cerebellum and spinal cord, there were substantial differences in the profiles of mosaicism. These results suggest that in SCA1 there is no clear causal relationship between the degree of somatic instability and selective neuronal vulnerability. The finding that somatic instability is most pronounced in the striatum of various knock-in models of polyglutamine diseases highlights the role of trans-acting tissue- or cell-specific factors in mediating the instability.  (+info)

TY - JOUR. T1 - Loss of Pol32 in Drosophila melanogaster causes chromosome instability and suppresses variegation. AU - Tritto, Patrizia. AU - Palumbo, Valeria. AU - Micale, Lucia. AU - Marzulli, Marco. AU - Bozzetti, Maria Pia. AU - Specchia, Valeria. AU - Palumbo, Gioacchino. AU - Pimpinelli, Sergio. AU - Berloco, Maria. PY - 2015/3/31. Y1 - 2015/3/31. N2 - Pol32 is an accessory subunit of the replicative DNA Polymerase δ and of the translesion Polymerase ζ. Pol32 is involved in DNA replication, recombination and repair. Pol32 s participation in high- and low-fidelity processes, together with the phenotypes arising from its disruption, imply multiple roles for this subunit within eukaryotic cells, not all of which have been fully elucidated. Using pol32 null mutants and two partial loss-of-function alleles pol32rd1 and pol32rds in Drosophila melanogaster, we show that Pol32 plays an essential role in promoting genome stability. Pol32 is essential to ensure DNA replication in early ...
Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood. CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in transcriptional regulation. Here, we used genome-wide ChIP sequencing and found that the DNA-bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. Adding cyclin D1 back to Ccnd1-/- mouse embryonic fibroblasts resulted in CIN gene regulatory region occupancy by the DNA-bound form of cyclin D1 and induction of CIN gene expression. Furthermore, increased chromosomal aberrations, aneuploidy, and centrosome abnormalities were observed in the cyclin D1-rescued cells by spectral karyotyping and immunofluorescence. To assess cyclin D1 effects in vivo, we generated transgenic mice with acute and continuous mammary gland-targeted cyclin D1 ...
Pericentromeric demethylation and chromosomal instability induced by chemicals. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
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This gene encodes an evolutionarily-conserved protein containing an N-terminal chromodomain and a C-terminal SET domain. The encoded protein is a histone methyltransferase that trimethylates lysine 9 of histone H3, which results in transcriptional gene silencing. Loss of function of this gene disrupts heterochromatin formation and may cause chromosome instability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013 ...
Chromosome instability (CIN) is an inherent enabling characteristic of cancer important for tumor initiation and progression and is observed in a majority of tumors (1⇓-3). It has been proposed that alterations resulting in genome instability happen early during tumor formation, allowing the accumulation of errors during DNA replication, repair, and chromosome segregation, thereby increasing the likelihood that a cell will acquire multiple genetic changes necessary for tumor progression (4). CIN is possibly the major contributor to intratumoral heterogeneity-that is, the presence of genetically distinct populations of cells within a single tumor that impacts treatment strategy, drug resistance, and tumor evolution (5⇓⇓-8). For these reasons, defining genes and pathways that drive CIN and understanding the mechanisms that underlie genome stability will contribute not only to an understanding of tumor etiology and progression but will also be relevant for guiding therapeutic strategies. The ...
Birkness JE, Spada NG, Miller C, Luketich JD, Nason KS, Sun W, Davison JM. Extreme chromosome 17 copy number instability is a prognostic factor in patients with gastroesophageal adenocarcinoma: A retrospective cohort study. Genes Chromosomes Cancer. 2018 01; 57(1):28-34 ...
By studying the role of lysosomes in mitosis, an IDIBELL and UB group discovers that alterations in the separation of chromosomes cause a detectable nucleus morphology once mitosis has finished.
Principal Investigator:YAMASHITA Takayuki, Project Period (FY):1999 - 2000, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Hematology
plays roles in the regulation of the HR activity and in chromosome stability, and is likely responsible for controlling the HR activity by directly interacting with RAD51 ...
Chromosome instability manifests as an abnormal chromosome complement and is a pathogenic event in cancer. Although a correlation between abnormal chromosome numbers and cancer exist, the underlying mechanisms that cause chromosome instability are poorly understood. Recent data suggests that aberrant sister chromatid cohesion causes chromosome instability and thus contributes to the development of cancer. Cohesion normally functions by tethering nascently synthesized chromatids together to prevent premature segregation and thus chromosome instability. Although the prevalence of aberrant cohesion has been reported for some solid tumors, its prevalence within liquid tumors is unknown. Consequently, the current study was undertaken to evaluate aberrant cohesion within Hodgkin lymphoma, a lymphoid malignancy that frequently exhibits chromosome instability. Using established cytogenetic techniques, the prevalence of chromosome instability and aberrant cohesion was examined within mitotic spreads generated
Centrosomes play critical roles in processes that ensure proper segregation of chromosomes and maintain the genetic stability of human cells. They contribute to mitotic spindle organization and regulate aspects of cytokinesis and cell cycle progression. We and others have shown that centrosomes are abnormal in most aggressive carcinomas. Moreover, centrosome defects have been implicated in chromosome instability and loss of cell cycle control in invasive carcinoma. Others have suggested that centrosome defects only occur late in tumorigenesis and may not contribute to early steps of tumor development. To address this issue, we examined pre-invasive human carcinoma in situ lesions for centrosome defects and chromosome instability. We found that a significant fraction of precursor lesions to some of the most common human cancers had centrosome defects, including in situ carcinomas of the uterine cervix, prostate, and female breast. Moreover, centrosome defects occurred together with mitotic spindle
Chromosomal instability (CIN) is a characteristic feature of cancer. In this review, we concentrate on mechanisms leading to CIN in myeloid neoplasia, i.e., myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The pathogenesis of myeloid neoplasia is complex and involves genetic and epigenetic alterations. Chromosome aberrations define specific subgroups and guide clinical decisions. Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. Indeed, disease progression is often driven by clonal evolution into complex karyotypes. Earlier studies have shown an association between telomere shortening and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and cancer. Several studies link chromosome rearrangements and aberrant DNA and histone methylation. Genes implicated in epigenetic control, like DNMT3A, ASXL1, EZH2 and TET2, have been
Chromosomal loss and rearrangement are known to be important signs of genetic instability in cancer cells, but the mechanisms behind these changes are unclear. We have begun an investigation of the contribution of segregational errors to chromosomal instability using oral carcinoma cells as our model system. In these cultures, we found frequent variations in chromosome numbers and structure between different cells from the same tumor cell culture. We believe that many of these abnormalities can be explained by chromosomal segregational defects.. The OSCC cells clearly had difficulty achieving normal metaphase alignment and anaphase chromosome separation. One simple model is that the kinetochores are defective for movement, and that this single defect causes chromosomes to lag at both metaphase and anaphase. Consistent with this model, approximately equal numbers of lagging chromosomes were observed in both metaphase and anaphase cells. One way to test this directly would be a real-time analysis ...
Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) is a form of GIN that involves frequent cytogenetic changes leading to changes in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics of cancer cells, their roles in tumor initiation and progression are unclear. On the one hand, CIN and aneuploidy are known to provide genetic variation to allow cells to adapt in changing environments such as nutrient fluctuations and hypoxia. Patients with constitutive aneuploidies are more susceptible to certain types of cancers, suggesting that changes in chromosome copy number could positively contribute to cancer evolution. On the other hand, chromosomal imbalances have been observed to have detrimental effects on cellular fitness and might trigger cell cycle arrest or apoptosis. Furthermore, mouse models for CIN have
TY - JOUR. T1 - Persistent chromosomal instability and cross-linker sensitivity in Fanconi anaemia derived leukaemia cell lines with bi-allelic FANCD1/BRCA2 mutations. AU - Meyer, S. AU - Tonnies, H. AU - Fergusson, WF. AU - Oostra, AB. AU - Medhurst, AL. AU - Waisfisz, Q. AU - De Winter, JP. AU - Chen, F. AU - Carr, TF. AU - Green, M. AU - Barber, L. AU - Eden, OB. AU - Will, AM. AU - Joenje, H. AU - Taylor, GM. PY - 2005/4. Y1 - 2005/4. M3 - Meeting Abstract. VL - 129. SP - 81. EP - 81. JO - British Journal of Haematology. JF - British Journal of Haematology. SN - 0007-1048. ER - ...
MYC copy gain, chromosomal instability and PI3K activation as potential markers of unfavourable outcome in trastuzumab-treated patients with metastatic breast cancer. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Hannes Alfvén. Plasma instabilities are not well-known to the general public, or among astronomers. They refer to distortions that occur when plasmas are generated and confined. They are often confused with phenomena observed in fluid interactions: Kelvin-Helmholtz instabilities, or Rayleigh-Taylor instabilities, for instance.. Since plasmas are conventional matter with a small percentage of ionized particles, they do not conform to kinetic energy principles, alone. Rather, matter in the plasma state is strongly influenced by electromagnetism, and does not obey any other force, including gravity, except peripherally. Many types of instability are observed in plasma: diocotron instabilities, kink instabilities, edge instabilities (that make fusion reactors impossible to control), sausage instabilities (deformations in plasma flow), reactive instabilities, etc.. A principle tenet of Electric Universe theory is that various plasmas (mostly hydrogen ions and helium nuclei) comprise 99.99% of the ...
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Read Chromosome instability and contents of heavy metals in amphibian from the Yugansk Reserve, Russian Journal of Ecology on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Centrosome abnormalities and amplification are common characteristics of tumour cells. Aneuploidy and chromosomal instability are highly correlated with the appearance of multiple centrosomes.. ...
Author(s): Spears, Melanie; Lyttle, Nicola; DCosta, Alister; Chen, Bingshu E; Yao, Cindy Q; Boutros, Paul C; Burnell, Margot; Levine, Mark N; OBrien, Patti; Shepherd, Lois; Bartlett, John MS | Abstract: Recent evidence demonstrated CIN4 as a predictive marker of anthracycline benefit in early breast cancer. An analysis of the NCIC CTG MA.21 clinical trial was performed to test the role of existing CIN gene expression signatures as prognostic and predictive markers in the context of taxane based chemotherapy.RNA was extracted from patients in cyclophosphamide, epirubicin and flurouracil (CEF) and epirubicin, cyclophosphamide and paclitaxel (EC/T) arms of the NCIC CTG MA.21 trial and analysed using NanoString technology.After multivariate analysis both high CIN25 and CIN70 score was significantly associated with an increased in RFS (HR 1.76, 95%CI 1.07-2.86, p=0.0018 and HR 1.59, 95%CI 1.12-2.25, p=0.0096 respectively). Patients whose tumours had low CIN4 gene expression scores were associated with an
Principal Investigator:TAKUBO Kaiyo, Project Period (FY):2009 - 2011, Research Category:Grant-in-Aid for Scientific Research (B), Section:一般, Research Field:Human pathology
We and others have demonstrated that TIF1γ was a tumor suppressor (24, 27-29), whose mechanism of action has remained elusive. In this study, we demonstrated that stable Tif1γ inactivation resulted in SAC and postmitotic checkpoint attenuation, leading to the accumulation of severe chromosomal abnormalities. As a result, Tif1γ-inactivated cells present mitotic defects increasing their tumor aggressiveness in animal models. Finally, we observed that low TIF1γ expression was associated with increased CIN in different types of human tumors. Therefore, this work highlights an original mechanism by which TIF1γ behaves as a tumor suppressor through its role in the control of mitosis, whose impairment may represent a major tumor-suppressive process.. First of all, we revealed here that the immediate consequence of TIF1γ depletion in different cell types (primary and immortalized MEFs, transformed or immortalized epithelial cells) resulted in a proliferation arrest, mitotic blockade, accumulation ...
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Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce …
The epigenetic framework guides events like replication, repair and transcription, which in turn themselves leave an imprint on chromatin and chromosomal structure. Understanding how modulation of chromatin during replication and repair influence cell fate decisions in normal development and disease represents a major challenge. By bringing together leading scientists in chromatin, replication, repair and epigenetics, this conference aims to inspire discussions and new ideas on the interplay between chromosome architecture, epigenetic inheritance and genome duplication ...
An experiment is performed to assess the prevalence of instability in univariate and bivariate macroeconomic time series relations and to ascertain whether various adaptive forecasting techniques successfully handle any such instability. Formal tests for instability and out-of-sample forecasts from sixteen different models are computed using a sample of 76 representative U.S. monthly postwar macroeconomic time series, constituting 5700 bivariate forecasting relations. The tests indicate widespread instability in univariate and bivariate autoregressive models. However, adaptive forecasting models, in particular time varying parameter models, have limited success in exploiting this instability to improve upon fixed-parameter or recursive autoregressive forecasts. ...
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Author: Perry Nickelston. Title: Five Hidden Signs of Instability. Summary: If you work with patients long enough, you come to realize a few in-the-trenches facts. Here are five biggies that require constant consideration...
Trouvez tous les livres de Schmeidler, Lacey - Instability, Liquidity and World Money. Sur eurolivre.fr,vous pouvez commander des livres anciens et neufs.COMPARER ET acheter IMMÉDIATEMENT au meilleur prix. 9783845404103
Haploids are a valuable tool for genomic studies in higher plants, especially those with huge genome size and long juvenile periods, such as conifers. In these species, megagametophyte cultures have been widely used to obtain haploid callus and somatic embryogenic lines. One of the main problems associated with tissue culture is the potential genetic instability of the regenerants. Because of this, chromosomal stability of the callus and/or somatic embryos should also be assessed. To this end, chromosome counting, flow cytometry and genotyping using microsatellites have been reported. Here, we present an overview of the work done in conifers, with special emphasis on the production of a haploid cell line in maritime pine (Pinus pinaster L.) and the use of a set of molecular markers, which includes Single Nucleotide Polymorphisms (SNPs) and microsatellites or Single Sequence Repeats (SSRs), to validate chromosomal integrity confirming the presence of all chromosomic arms.
TY - JOUR. T1 - Mechanisms and consequences of aneuploidy and chromosome instability in the aging brain. AU - Andriani, Grasiella A.. AU - Vijg, Jan. AU - Montagna, Cristina. N1 - Funding Information: C.M. and J.V. work is partially supported by grants from the National Institutes of Health [AG017242 to J.V] and from the Albert Einstein Cancer Center Support Grant of the National Institutes of Health [P30CA013330]. Publisher Copyright: © 2016 Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2017/1/1. Y1 - 2017/1/1. N2 - Aneuploidy and polyploidy are a form of Genomic Instability (GIN) known as Chromosomal Instability (CIN) characterized by sporadic abnormalities in chromosome copy numbers. Aneuploidy is commonly linked to pathological states. It is a hallmark of spontaneous abortions and birth defects and it is observed virtually in every human tumor, therefore being generally regarded as detrimental for the development or the maturation of tissues under physiological ...
The Chromatin, Replication and Chromosomal Stability Conference took place on June 20-21 in Stockholm, Sweden. In this article, I outline the broad scientific program of the meeting which reflected the wide diversity in epigenetics research. Distinct histone modifications are linked with specific chromatin structures and intranuclear positioning, thereby impacting replication timing and replication initiation, which in turn are related to gene expression and cell differentiation. Interference in any of these interconnected mechanisms can result in DNA breakage and lead to the activation of repair pathways. The DNA repair mechanisms again are influenced by the chromatin structure. In summary, the conference highlighted the functional implication of epigenetics in chromatin compaction, transcription regulation, replication control and DNA repair. The tight control of all these mechanisms defines the final cellular character.
Many cancers have extremely high rates of chromosomal instability (CIN). Some cancers have chromosome segregation errors in every cell division, which would be detrimental to the growth of normal cells. Little is known about how cancers are able to thrive with high levels of CIN. We aim to determine how cells evolve to cope with CIN by creating a model system for persistent chromosomal instability in budding yeast. What types of mutations allow cells to adapt to a constantly shifting genomic content? What are the direct effects of CIN and aneuploidy on the health and viability of cells?. ...
Chromosomal instability has long been recognized as a hallmark of cancer. Cancer progresses as cells override the intrinsic system of checks and balances that normally prevents them from dividing in the presence of a damaged or aneuploid genome. Chromosomal instability is described as increased chromosome missegregation and often results in aneuploidy or the condition of having too many or too few chromosomes. Under normal physiologic conditions, cell-cycle traverse is carefully controlled by sequential posttranslational modifications, especially E3 ligase-mediated ubiquitination (1, 2). The anaphase-promoting complex/cyclosome (APC/C) is a major E3 ligase complex that promotes the metaphase-to-anaphase transition, and its activation is inhibited until surveillance mechanisms within the cell sense proper metaphase alignment and bipolar spindle attachment of chromosomes (2, 3). Activation of the APC/C occurs via interaction with a cofactor that confers specificity to the complex, either FZR1/CDH1 ...
Many cancers have extremely high rates of chromosomal instability (CIN). Some cancers have chromosome segregation errors in every cell division, which would be detrimental to the growth of normal cells. Little is known about how cancers are able to thrive with high levels of CIN. We aim to determine how cells evolve to cope with CIN by creating a model system for persistent chromosomal instability in budding yeast. What types of mutations allow cells to adapt to a constantly shifting genomic content? What are the direct effects of CIN and aneuploidy on the health and viability of cells? close ...
In a new study, Dana-Farber Cancer Institute scientists disprove a century-old theory about why cancer cells often have too many or too few chromosomes, and show that the actual reason may hold the key to a novel approach to cancer therapy.. Since the late 19th century, scientists have attributed the surplus or shortage of intact chromosomes in cancer cells to a kind of fragmentation in cell division: instead of dividing neatly into two identical daughter cells, as normal cells do, cancer cells were thought to frequently split into three or four cells, each with a motley assortment of chromosomes. This explosive division was thought to occur because many cancer cells have extra centrosomes, tiny circular structures that help pairs of chromosomes line up in preparation for cell division.. When study lead author Neil Ganem, PhD, of Dana-Farber used newly developed microscope equipment to watch living cancer cells for a week or more, he found that not only were such abnormal divisions quite rare, ...
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The purpose of this study was to analyze the impact of copy number variations (CNV) on sporadic pituitary neuroendocrine tumors (PitNETs) prognosis, to identify specific prognosis markers according to the known clinico-pathological classification. CGH array analysis was performed on 195 fresh-frozen …
NEW YORK, N.Y. (SEND2PRESS NEWSWIRE) -- The Sher Institutes of Reproductive Medicine (SIRM) announced today the introduction of the worlds first CGH-Risk Sharing Plan that guarantees qualified IVF patients a baby or offers a full refund of the clinics medical fees. CGH is an acronym for Comparative Genomic Hybridization - a genetic process that analyzes the chromosomal integrity of the egg or embryo prior to it being transferred to a womans uterus in the course of In Vitro Fertilization. - News from Sher Institute for Reproductive Medicine, issued by Send2Press Newswire
DNA ISH can be used to determine the structure of chromosomes. Fluorescent DNA ISH (FISH) can, for example, be used in medical diagnostics to assess chromosomal integrity. RNA ISH (hybridization histochemistry) is used to measure and localize mRNAs and other transcripts within tissue sections or whole mounts. ...
Ren, Y.; Lv, Q.; Yue, W.; Liu, B.; Zou, Z., 2019: The programmed cell death protein-1/programmed cell death ligand 1 expression, CD3+ T cell infiltration, NY-ESO-1 expression, and microsatellite instability phenotype in primary cutaneous melanoma and mucosal melanoma and their clinical significance and prognostic value: a study of 89 consecutive cases
UniSA researchers at the Centre for Cancer Biology (CCB) have discovered a new aspect of cancer biology that may help to battle the spread and growth of tumours.. The research focuses on aneuploid cells, which are often associated with abnormal chromosome content and cell division - and how an enzyme known as caspase-2, initially discovered by the lead researcher 25 years ago, can act to prevent their growth.. Research leaders, Professor Sharad Kumar and Dr Loretta Dorstyn with PhD student Swati Dawar, have discovered that caspase-2, which is found in all mammals, has the capacity to suppress cancer growth by working to destroy aneuploid cells.. Aneuploidy is a term that describes the abnormal chromosome content of a cell and occurs when there are failings during the normal division of a cell, Prof Kumar says.. Aneuploidy is a feature of the majority of human tumours and is known to lead to chromosomal instability that can promote cancer onset and progression and cause drug ...
Structures of thin films bonded on thick substrates are abundant in biological systems and engineering applications. Mismatch strains due to expansion of the films or shrinkage of the substrates can induce various modes of surface instabilities such as wrinkling, creasing, period doubling, folding, ridging, and delamination. In many cases, the film-substrate structures are not flat but curved. While it is known that the surface instabilities can be controlled by film-substrate mechanical properties, adhesion and mismatch strain, effects of the structures curvature on multiple modes of instabilities have not been well understood. In this paper, we provide a systematic study on the formation of multimodal surface instabilities on film-substrate tubular structures with different curvatures through combined theoretical analysis and numerical simulation. We first introduce a method to quantitatively categorize various instability patterns by analyzing their wave frequencies using fast Fourier ...
One-dimensional thermodynamic instabilities are phase transitions, not prohibited by Landaus argument because the energy of the domain wall which separates the two phases is infinite. Whether they actually occur in a given system of particles must be demonstrated on a case-by-case basis by examining the properties of the corresponding singular transfer integral (TI) equation. The present work deals with the generic Peyrard-Bishop model of DNA denaturation. In the absence of exact statements about the spectrum of the singular TI equation, I use Gauss-Hermite quadratures to achieve a single-parameter-controlled approach to rounding effects; this allows me to employ finite-size scaling concepts in order to demonstrate that a phase transition occurs and to derive the critical exponents.
Abstract: Supposing there exists no new physics stabilizing the weak scale, the Standard Model Higgs potential exhibits a true vacuum at large field values, rendering the electroweak vacuum metastable (i.e., long lived relative to the age of the Universe). While this scenario need not preclude our current existence, it may not reconcile with a period of large(ish)-field inflation---large fluctuations in the Higgs field, induced by the inflationary energy density, can lead to the field locally sampling the unstable/true vacuum part of the potential, with potentially disastrous consequences. Evaluating the extent to which large-field inflation and the Higgs vacuum instability are incompatible requires understanding (i) how Higgs fluctuations evolve during inflation and (ii) the fate of large local fluctuations that sample the part of the potential beyond the barrier that separates the electroweak and true vacua. In this talk, I will discuss both of these aspects, and explain the implications for ...
Instabilities in polymer processing limit production rates and may influence to some degree the optical or mechanical properties of the final product. One prominent example is the fountain flow instability, which takes place during the mold filling stage of an injection molding process. Old car bumpers which show light and dark lines are a famous example of an injection molded part in which such an instability occurred.
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is negative, one expects curvature instabilities of the membrane and, in turn, these instabilities generate a pattern of domains that differ both in composition and in local curvature. Scaling arguments motivate the study of the family of singular perturbed energies ...
Strategies the pa- tient has used to reduce risk for infection are identified.1994; Zwangersschap and Shine, 1992; Mishima et al.
that instability can occur even after the full establishment of the primary flow. Chandrasekhars method is used in the analysis and the relationship between the stability parameter and the wave number of the disturbance for neutral stability is obtained.--Page 1 ...
2019 marks a year of instability and uncertainty reflected in the field of potential best picture nominees, from Parasite to Joker.
found that rearrangements involving telomere regions are associated with chromosomal instability in human fibroblasts that ... "Chromosomal instability". Nature. 357 (6379): 548. Bibcode:1992Natur.357..548S. doi:10.1038/357548a0. PMID 1608466. S2CID ... Genomic instability has been observed both in vitro and in vivo in the progeny of cells that are irradiated with heavy ions in ... In fact, only a small fraction of the initial damage is transduction of late chromosomal damage has also been measured in the ...
Boukamp, Petra; Popp, Susanne; Krunic, Damir (2005-11-01). "Telomere-Dependent Chromosomal Instability". Journal of ... which are rotations in regions of a chromosome due to chromosomal breakages or intra-chromosomal recombinations. Inversions ... Chromosomal inversion Telomeres Cytogenetics Nuclear radiation Intellectual disorders Nussbaum, Robert; McInnes, Roderick; ... Pseudodicentric chromosomes alone do not define these syndromes, because the contribution of other chromosomal abnormalities ...
"Metabolic aggressiveness in benign meningiomas with chromosomal instabilities". Cancer Research. 70 (21): 8426-8434. doi: ...
Chromosomal instability resulting from dysfunctional caretaker genes is the most common form of genetic instability that leads ... mutational instability arising from changes in the nucleotide sequence of DNA and chromosomal instability arising from improper ... Michor, F; Iwasa, Y; Komarova, N. L.; Nowak, M. A. (2003). "Local regulation of homeostasis favors chromosomal instability". ... Van Gent, D. C.; Hoeijmakers, J. H.; Kanaar, R (2001). "Chromosomal stability and the DNA double-stranded break connection". ...
Walther, A.; Houlston, R.; Tomlinson, I. (2008-07-01). "Association between chromosomal instability and prognosis in colorectal ... "Chromosomal instability is a risk factor for poor prognosis of adenocarcinoma of the lung: Fluorescence in situ hybridization ... "Chromosomal Instability Confers Intrinsic Multi-Drug Resistance". Cancer Research. 71 (5): 1858-1870. doi:10.1158/0008-5472.CAN ... "Cancer chromosomal instability: therapeutic and diagnostic challenges". EMBO Reports. 13 (6): 528-538. doi:10.1038/embor. ...
McGranahan N, Burrell RA, Endesfelder D, Novelli MR, Swanton C (June 2012). "Cancer chromosomal instability: therapeutic and ... high chromosomal instability can act as a tumor-suppressing mechanism by leading to cell death. Therefore, the significant ... The instability and drop in TPX2 at mitotic exit is dependent on both the anaphase-promoting complex/cyclosome (APC/C) and an ... A result of this decrease is a defect in BP531 (p53 binding protein 1) recruitment to chromosomal breaks, as recruitment is ...
December 2014). "Mutant cohesin drives chromosomal instability in early colorectal adenomas". Human Molecular Genetics. 23 (25 ... Genome instability and cancer[edit]. SMC1A also takes part in DNA repair. The down-regulation of SMC1A causes genome ... Yatskevich S, Rhodes J, Nasmyth K (December 2019). "Organization of Chromosomal DNA by SMC Complexes". Annual Review of ... June 2003). "Inhibition of BUB1 results in genomic instability and anchorage-independent growth of normal human fibroblasts". ...
Castagnola P, Giaretti W (November 2005). "Mutant KRAS, chromosomal instability and prognosis in colorectal cancer". Biochimica ...
DCC would fall into the chromosomal instability category. The chromosomal region of 18q has shown consistent LOH for nearly ... The first was a chromosomal instability pathway thought to be responsible for the adenoma to carcinoma progression, which was ... Loss of DCC in colorectal cancer primarily occurs via chromosomal instability, with only a small percent having epigenetic ... but cancer related genes still tend to be categorized as chromosomal or microsatellite instability genes. ...
"Potential role of meiosis proteins in melanoma chromosomal instability". Journal of Skin Cancer. 2013: 190109. doi:10.1155/2013 ... "Potential Role of Meiosis Proteins in Melanoma Chromosomal Instability". Journal of Skin Cancer. 2013: 190109. doi:10.1155/2013 ... Ross, Andrew L.; Leder, Daniel E.; Weiss, Jonathan; Izakovic, Jan; Grichnik, James M. (September 2011). "Genomic instability in ... "A study of meiomitosis and novel pathways of genomic instability in cutaneous T-cell lymphomas (CTCL)". Oncotarget. 9 (102): ...
"Chromosomal instability drives metastasis through a cytosolic DNA response". Nature. 553 (7689): 467-472. doi:10.1038/ ...
... (NBS), is a rare autosomal recessive congenital disorder causing chromosomal instability, probably ... "A new chromosomal instability disorder: the Nijmegen breakage syndrome". Acta Paediatr Scand. 70 (4): 557-64. doi:10.1111/j. ... chromosome instability and fertility defects, but not the developmental defects that are typically found in other NBS patients ...
"Centrosome amplification drives chromosomal instability in breast tumor development". Proc Natl Acad Sci USA. 99 (4): 1978-1983 ... The presence of an inadequate number of centrosomes is very often linked to the appearance of genome instability and the loss ... Storchova, Z.; Pellman, D. (2004). "From polyploidy to aneuploidy, genome instability and cancer". Nat Rev Mol Cell Biol. 5 (1 ... "Centrosome amplification and instability occurs exclusively in aneuploid, but not in diploid colorectal cancer cell lines, and ...
It usually is a sign of genotoxic events and chromosomal instability. Micronuclei are commonly seen in cancerous cells and may ... extremely versatile and is one of the preferred methods to measure the level of chromosomal damage and chromosomal instability ... The frequencies of chromosomal aberrations, damaged cells, and micronuclei are significantly higher in smokers than non-smokers ... The major drawback of using micronucleus tests is that they cannot determine different types of chromosomal aberrations and can ...
October 2014). "Mechanism of suppression of chromosomal instability by DNA polymerase POLQ". PLOS Genetics. 10 (10): e1004654. ... Sharief FS, Vojta PJ, Ropp PA, Copeland WC (July 1999). "Cloning and chromosomal mapping of the human DNA polymerase theta ( ... "A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites". Nature ...
Produces extracellular superoxide under selected growth conditions that can generate chromosomal instability in mammalian cells ... "Extracellular Superoxide Production by Enterococcus faecalis Promotes Chromosomal Instability in Mammalian Cells". ...
... as well as chromosomal instability. MCM9, as well as MCM8, mutations are also associated with ovarian failure and chromosomal ... January 2015). "Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability". The Journal of ... December 2014). "MCM9 mutations are associated with ovarian failure, short stature, and chromosomal instability". American ... instability. The MCM8-MCM9 complex is likely required for the homologous recombinational repair of DNA double-strand breaks ...
"Overexpression of BUBR1 is associated with chromosomal instability in bladder cancer". Cancer Genetics and Cytogenetics. 174 (1 ... also known as genome instability. Genomic integrity is now appreciated at several levels where some tumors display instability ... That is, defects such as an increase in DNA damage, chromosomal rearrangements, and/or a decreased incidence of cell death. For ... According to some observations, a fraction of cohesins in the chromosomal arms and the centromeric cohesins are protected by ...
This can lead to loss of cell viability and chromosomal instability. The presence of multipolar spindles in cancer cells is one ... Mitosis consists of two independent processes: the intra-chromosomal and the extra-chromosomal (formation of spindle) changes ...
"Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin". Science. 327 (5962): 172-7. doi: ...
Chromosomal rearrangement due to genome instability can cause gene amplification and deletion. Gene amplification is the ... Genomic instability can occur when the replication fork is disturbed or stalled in its migration. This can occur with ... This genomic instability means the cancer cell is actually more sensitive to DNA-damaging chemotherapy drugs. MDR proteins are ... Histone modifications, such as deacetylation, alters chromatin formation and silence large chromosomal regions. In cancer cells ...
2004). "Chfr inactivation is not associated to chromosomal instability in colon cancers". Oncogene. 22 (55): 8956-60. doi: ...
March 2012). "ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice". The Journal of ... April 2015). "Kinase-independent role of cyclin D1 in chromosomal instability and mammary tumorigenesis". Oncotarget. 6 (11): ... induction of chromosomal instability, restraint of autophagy and potentially non-canonical functions. Overexpression is induced ... or chromosomal translocation. Gene amplification is responsible for overproduction of cyclin D protein in bladder cancer and ...
Pihan, G. a. (2013). Centrosome dysfunction contributes to chromosome instability, chromoanagenesis, and genome reprograming in ... complex chromosomal rearrangements. Nature Medicine, 18(11), 1630-8. doi:10.1038/nm.2988 Haffner, M. C., Aryee, M. J., Toubaji ... a catch-all term for events that generate complex structural chromosomal abnormalities. The mechanism underlying complex ... rapid genome evolution from complex chromosomal rearrangements. Genes & Development, 27(23), 2513-30. doi:10.1101/gad. ...
Chromosome instability syndromes are a group of disorders characterized by chromosomal instability and breakage. They often ... A chromosome abnormality, disorder, anomaly, aberration, or mutation is a missing, extra, or irregular portion of chromosomal ... Chromosome mutation was formerly used in a strict sense to mean a change in a chromosomal segment, involving more than one gene ... Governini L, Guerranti C, De Leo V, Boschi L, Luddi A, Gori M, Orvieto R, Piomboni P (2014). "Chromosomal aneuploidies and DNA ...
"The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells". Proc Natl Acad Sci U S A. ... Stolz A, Ertych N, Bastians H (2011). "Tumor suppressor CHK2: regulator of DNA damage response and mediator of chromosomal ...
Micronuclei are usually a sign of genotoxic events and chromosomal instability (see Micronucleus). 8-dihydro-2'-deoxyguanosine ...
These mice exhibit chromosomal instability, indicating that NHEJ is important for genome maintenance. In many organisms, Ku has ... "DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation". Nature. 404 (6777): 510-4. Bibcode: ...
Bolzán AD (December 2020). "Using telomeric chromosomal aberrations to evaluate clastogen-induced genomic instability in ... Upon exposure to clastogens, the effects seen can consist of chromosomal rearrangements. The portions of deletions or ... Clastogens (which break chromosomes) contribute to telomeric instability because it leads to chromosome end loss or true ... Bignold, L.P. (March-June 2009). "Mechanisms of clastogen-induced chromosomal aberrations: A critical review and description of ...
Political instability and local feuds, aggravated by the poverty of the dispossessed Marsh Arab population, remain a serious ... Y-chromosomal Aaron. *Y-DNA haplogroups in populations of the Near East ...
"Chromosomal instability in gastric mucosa-associated lymphoid tissue lymphomas: A fluorescent in situ hybridization study using ... Currently, this type of analysis will only detect gains and losses of chromosomal material and will not detect balanced ... FISH is used by examining the cellular reproduction cycle, specifically interphase of the nuclei for any chromosomal ... due to subtle chromosomal features; FISH can elucidate these differences. FISH can also be used to detect diseased cells more ...
"Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens". Mutation ... Radiation-Induced Genomic Instability and Bystander Effects Clastogenic Factors and Transgenerational Effects". Radiation ... It has been shown that radiation damage including genome instability and carcinogenesis may occur transgenerationally in both ... "Epigenetic dysregulation underlies radiation-induced transgenerational genome instability in vivo". International Journal of ...
"Huang R C & Bonner J. Histone, a suppressor of chromosomal RNA synthesis. Proc. Nat. Acad. Sci. US 48:1216-22, 1962" (PDF). ... "Genomic instability in mice lacking histone H2AX". Science. 296 (5569): 922-7. Bibcode:2002Sci...296..922C. doi:10.1126/ ... Hannon Bozorgmehr J (Oct 2019). "The origin of chromosomal histones in a 30S ribosomal protein". Gene. doi:10.1016/j.gene. ... "Histone, a suppressor of chromosomal RNA synthesis". Proceedings of the National Academy of Sciences of the United States of ...
Numerical and structural chromosomal aberrations identified by SKY, genomic imbalances detected by CGH, as well as FISH ... does not fulfill the criteria for an independent unicellular asexually reproducing species because of the notorious instability ... "Enzymatic and chromosomal characterization of HeLa variants". J. Cell Biol. 41 (3): 806-15. doi:10.1083/jcb.41.3.806. PMC ...
... and displayed chromosomal instability in a micronucleus test.[29] MCPH1 is involved in the ATM and ATR-mediated DNA damage ... thus increasing genomic instability.[37] MCPH1 facilitation of the DNA damage response appears to be necessary for proper ...
Such alterations are thought to occur early in progression to cancer and to be a likely cause of the genetic instability ... Genomic amplification occurs when a cell gains copies (often 20 or more) of a small chromosomal locus, usually containing one ... Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well- ... links to genetic instability". Carcinogenesis (review). 30 (7): 1073-81. doi:10.1093/carcin/bgp127. PMID 19468060.. ...
... cells of affected individuals exhibit chromosomal abnormalities, genomic instability, and sensitivity to mutagens.[7] ... Defective homologous recombination can cause mutation and genetic instability.[27] Such defective recombination can introduce ... "Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780-5. doi:10.1038/nm1266. PMID 15980864.. ... which is caused by genomic instability and increased rates of mutation.[7] ...
Studies show that in cases of cancer and other genomic instability, higher levels of EEs can be observed. Mitochondrial DNA can ... Certain organisms, such as yeast, rely on chromosomal DNA replication to produce eccDNA whereas eccDNA formation can occur in ... Small polydispersed DNAs (spcDNAs) are commonly found in conjunction with genome instability. SpcDNAs are derived from ... Double minute chromosomes (DMs) are also extrachromosomal elements that are associated with genome instability. DMs are ...
Epigenetic reductions of DNA repair enzyme expression may likely lead to the genomic and epigenomic instability characteristic ... direct hypermethylation or hypomethylation of CpG islands of protein-encoding genes and alterations in histones and chromosomal ... a survey of current practices and re-evaluation of the role of microsatellite instability testing". Modern Pathology. 31 (11): ... "High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of ...
இது ஒரு வகையான பரம்பரை அலகுகளில் (gene or in chromosomal DNA region) ஏற்படும் மாற்றங்களினால் அல்லது டி.என்.ஏ க்களில் பிறழ்வுகளை ... "Hypoxia and defective apoptosis drive genomic instability and tumorigenesis". Genes & Development 18 (17): 2095-107. doi ...
At the present time, there is no specific treatment that can undo any chromosomal abnormality, nor the genetic pattern seen in ... However, mostly because of the marker's instability and tendency to be lost during cell division (mitosis), some cells are ... A chromosome anomaly involves extra or missing chromosomal material, not changes within the genes such as Fragile X syndrome). ... Some individuals show other signs that can often be associated with chromosomal conditions, such as pectus excavatum, or a ...
2005). "Repeat instability: mechanisms of dynamic mutations". Nature Reviews Genetics. 6 (10): 729-742. doi:10.1038/nrg1689.. ... Microsatellites are used for assessing chromosomal DNA deletions in cancer diagnosis. Microsatellites are widely used for DNA ... This is likely due to homologous chromosomes with arms of unequal lengths causing instability during meiosis.[19] ... Amos W, Rubinsztein DC (1996). "Microsatellites show mutational bias and heterozygote instability". Nature Genetics. 13: 390- ...
It started in Toledo in 1449, in a period of political instability, when King John I sent his constable Don Alvaro de Luna to ... "Tracing Past Human Male Movements in Northern/Eastern Africa and Western Eurasia: New Clues from Y-Chromosomal Haplogroups E- ... "Tracing Past Human Male Movements in Northern/Eastern Africa and Western Eurasia: New Clues from Y-Chromosomal Haplogroups E- ...
She noticed chromosomal insertions, deletions, and translocations caused by these elements. These changes in the genome could, ... retrotransposition and genome instability". Cell. 110 (3): 277-80. doi:10.1016/S0092-8674(02)00868-1. PMID 12176313. ... Multiple copies of the same sequence, such as Alu sequences, can hinder precise chromosomal pairing during mitosis and meiosis ... In bacteria, transposons can jump from chromosomal DNA to plasmid DNA and back, allowing for the transfer and permanent ...
This instability makes defining the exact affinity of PGI2 for IP difficult. It also makes it important to have stable ... Duncan AM, Anderson LL, Funk CD, Abramovitz M, Adam M (February 1995). "Chromosomal localization of the human prostanoid ... "Structural organization and chromosomal assignment of the human prostacyclin receptor gene". Genomics. 27 (1): 142-8. doi: ...
Chambers, Sarah C. (2003). "Little Middle Ground The Instability of a Mestizo Identity in the Andes, 18th and 19th centuries". ... "Inferring Continental Ancestry of Argentineans from Autosomal, Y-Chromosomal and Mitochondrial DNA". Annals of Human Genetics ... Chambers, Sarah C. (2003). "Little Middle Ground The Instability of a Mestizo Identity in the Andes, 18th and 19th centuries". ... international political instability was a key factor to drive immigration to Mexico; in this era Greeks, Romanians, Portuguese ...
The term episome was introduced by François Jacob and Élie Wollman in 1958 to refer to extra-chromosomal genetic material that ... DNA structural instability can be defined as a series of spontaneous events that culminate in an unforeseen rearrangement, loss ... A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can ... Yeast Replicative Plasmid (YRp), which transport a sequence of chromosomal DNA that includes an origin of replication. These ...
Lindahl T (April 1993). "Instability and decay of the primary structure of DNA". Nature. 362 (6422): 709-15. Bibcode:1993Natur. ... Chromosomal crossover is when two DNA helices break, swap a section and then rejoin. ... Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. ... The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very ...
"Chromosomal instability drives metastasis through a cytosolic DNA response". Nature. 553 (7689): 467-472. Bibcode:2018Natur.553 ... Recent work identified a form of genetic instability in cancer called chromosome instability (CIN) as a driver of metastasis.[ ...
The chromosomal defect in the Philadelphia chromosome is a reciprocal translocation, in which parts of two chromosomes, 9 and ... Moreover, it inhibits DNA repair, causing genomic instability and potentially causing the feared blast crisis in CML. ... Rowley JD (1973). "Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine ... this chromosomal translocation is designated as t(9;22)(q34;q11). The symbol ABL is derived from Abelson, the name of a ...
Chromosomal aberrations involving this gene are associated with left-right axis malformation and mutations in this gene have ... "Manipulation of nonsense mediated decay identifies gene mutations in colon cancer Cells with microsatellite instability". ...
... and chromosomal instability in tumor growth and spread.[7] Sager was one of the first people to emphasize the importance of ...
The resulting thermal instability driven convective flow automatically shuffles the PCR reagents from the hot and cold regions ... has greatly enhanced the more traditional task of genetic mapping by studying chromosomal crossovers after meiosis. Rare ...
de Grouchy J, de Nava C (August 1968). "A chromosomal theory of carcinogenesis". Ann. Intern. Med. 69 (2): 381-91. doi:10.7326/ ... System instability is a major contributing factor for genetic heterogeneity.[42] For the majority of cancers, genome ... De Grouchy J.; de Nava C. (1968). "A chromosomal theory of carcinogenesis". Ann Intern Med. 69: 381-91. doi:10.7326/0003-4819- ... In the decades that followed, cancer was recognized as having a clonal origin associated with chromosomal aberrations.[9][10][ ...
... are in a state of instability promoting their progression towards anaphase.[17] At this point, the chromosomes are ready to ... protective sequences of DNA on the end of a chromosome that prevent degradation of the chromosomal DNA, shorten. This ...
... expression and chromosomal localization". Biochim Biophys Acta. 1444 (3): 346-54. PMID 10095058. doi:10.1016/S0167-4781(99) ... messenger RNA stability is regulated by cis-acting instability elements present in the 3'-untranslated region.". Biochim. ...
The most common chromosomal aneuploidy is a trisomy of chromosome 21 which manifests itself as Down syndrome. Current ... DNA fragment analysis can also be used to determine such disease causing genetics aberrations as microsatellite instability ( ... "SoftGenetics Application Note - Microsatellite Instability Analysis with GeneMarker® Tamela Serensits" (PDF). SoftGenetics. ...
Caire, William; Zimmerman, Earl G. (1975). "Chromosomal and Morphological Variation and Circular Overlap in the Deer Mouse, ... and fragmented populations due to climate instability have also been cited.[10] ...
Chromosomal instability determines taxane response.. Swanton C1, Nicke B, Schuett M, Eklund AC, Ng C, Li Q, Hardcastle T, Lee A ... lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability ( ... A) Quantification of gene repression following paclitaxel treatment of cell lines with increasing chromosomal numerical ... Colorectal cancer cell lines with increasing chromosomal numerical heterogeneity uncouple mitotic arrest from cell death. Cell ...
Chromosomal instability and cytoskeletal defects in oral cancer cells. William S. Saunders, Michele Shuster, Xin Huang, Burhan ... Chromosomal instability and cytoskeletal defects in oral cancer cells. William S. Saunders, Michele Shuster, Xin Huang, Burhan ... Chromosomal instability and cytoskeletal defects in oral cancer cells Message Subject (Your Name) has sent you a message from ... Chromosomal instability and cytoskeletal defects in oral cancer cells. William S. Saunders, Michele Shuster, Xin Huang, Burhan ...
According to Pellman, chromosomal instability, it turns out, "is actually a side effect of the cells ability to cluster their ... Link Unraveled Between Chromosomal Instability, Centrosome Defects In Cancer Cells. by Sam Savage ... but the correction process creates other problems that result in chromosomal instability." ... "Such instability may be a double-edged sword. It may confer a survival benefit on cancer cells by enabling them to adapt to a ...
Another common finding in cancer cells is chromosomal instability, a condition in which cells change their chromosomal content ... Whole chromosome gain does not in itself confer cancer-like chromosomal instability. Anders Valind, Yuesheng Jin, Bo Baldetorp ... It is clear that chromosomal instability can lead to aneuploidy, but whether the opposite is true has been much debated in the ... Here, we show that aneuploidy does not, on its own, lead to chromosomal instability, even when cells acquire chromosome ...
Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here ... Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. ... Chromosomal instability drives metastasis through a cytosolic DNA response Nature. 2018 Jan 25;553(7689):467-472. doi: 10.1038/ ... Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here ...
... Nat Commun. 2018 Aug 1;9(1):3012. doi: ... in the presence of increased rates of chromosome instability. In patients, Plk1 overexpression correlates with improved ...
Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice.. Theunissen JW1, Kaplan MI, ... The mice also exhibited pronounced chromosomal instability. Despite this phenotypic spectrum, the animals were not prone to ... These data indicate that defective cell cycle checkpoints and chromosomal instability are insufficient to significantly enhance ... We propose that in Mre11(ATLD1/ATLD1) mice, genome instability and cell cycle checkpoint defects reduce viability in early ...
This is called chromosomal instability, and scientists at Memorial Sloan Kettering have learned that it is associated with ... Researchers discover how chromosomal instability allows cancer cells to avoid immune defenses. *Download PDF Copy ... This is called chromosomal instability, and scientists at Memorial Sloan Kettering have learned that it is associated with ...
Chromosomal Instability Confers Intrinsic Multidrug Resistance. Alvin J.X. Lee, David Endesfelder, Andrew J. Rowan, Axel ... Chromosomal Instability Confers Intrinsic Multidrug Resistance. Alvin J.X. Lee, David Endesfelder, Andrew J. Rowan, Axel ... Chromosomal Instability Confers Intrinsic Multidrug Resistance. Alvin J.X. Lee, David Endesfelder, Andrew J. Rowan, Axel ... The more common form of genomic instability in CRC is chromosomal instability (CIN), resulting in ongoing numerical and ...
CFSs are chromosomal regions that are stable under normal conditions but display an increased rate of breakage under ... In particular, they are preferential sites for chromosomal aberrations, viral DNA integration and are linked to the onset of ... The mechanisms responsible for CFS instability are hotly debated but different models all point to their inability to complete ... leading to chromosome breakage and genome instability. A large subset of these hard to replicate regions are referred to as ...
Chromosomal Instability: An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome ... Instabilities, Chromosomal; Instabilities, Chromosome; Instability, Chromosomal; Instability, Chromosome; Stabilities, ... Chromosome Stability; Chromosomal Stability; Chromosome Instability; Chromosomal Instabilities; Chromosomal Stabilities; ... Chromosomal Instability (Chromosome Stability). Subscribe to New Research on Chromosomal Instability An increased tendency to ...
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The aneuploid index was calculated as the sum of all the consistent chromosomal gains or losses present in the karyotype. Thus ...
Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible ... Clearly, genetic instability and clonal evolution are driving forces for leukemic transformation. Understanding the mechanisms ... Chromosomal instability (CIN) is a characteristic feature of cancer. In this review, we concentrate on mechanisms leading to ... and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and ...
... July 07, 2020. A team from the Bellvitge ... Toroidal nucleus, a new biomarker of chromosomal instability. This study describes, for the first time, that cells that have ... Until now, the only biomarker to determine chromosomal instability was the micronucleus. The work led by Dr. Mauvezin presents ... This particular morphology represents a potential new biomarker for the identification of cells with chromosomal instability.. ...
Unravelling chromosomal instability in mammalian preimplantation embryos using single-cell genomics ... Olga Tšuiko „Unravelling chromosomal instability in mammalian preimplantation embryos using single-cell genomics". ... Olga Tšuiko „Unravelling chromosomal instability in mammalian preimplantation embryos using single-cell genomics" ... On 26 November at 15 Olga Tšuiko will defend her doctoral thesis „Unravelling chromosomal instability in mammalian ...
RAD51 Mutants Cause Replication Defects and Chromosomal Instability. Tae Moon Kim, Jun Ho Ko, Lingchuan Hu, Sung-A Kim, ... RAD51 Mutants Cause Replication Defects and Chromosomal Instability. Tae Moon Kim, Jun Ho Ko, Lingchuan Hu, Sung-A Kim, ... RAD51 Mutants Cause Replication Defects and Chromosomal Instability. Tae Moon Kim, Jun Ho Ko, Lingchuan Hu, Sung-A Kim, ... RAD51 Mutants Cause Replication Defects and Chromosomal Instability Message Subject (Your Name) has forwarded a page to you ...
Gene mutation rates (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and genomewide DNA methylation ... Differential Pathogenesis of Lung Adenocarcinoma Subtypes Involving Sequence Mutations, Copy Number, Chromosomal Instability, ...
Chromosomal and microsatellite instability in colorectal cancer (Homo sapiens). From WikiPathways. Revision as of 11:47, 15 ... Pino MS, Chung DC; The chromosomal instability pathway in colon cancer.; Gastroenterology, 2010 PubMed Europe PMC Scholia* ... The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of ... Genomic instability. Inactivating mutation. CSNK1A1L. CSNK1A1. CTNNB1. P. P. P. Survival. EXOC2. TBK1. REL. Cell-survival. ...
Chromosomal and microsatellite instability in colorectal cancer (Homo sapiens). From WikiPathways. Revision as of 19:20, 12 ... Pino MS, Chung DC; The chromosomal instability pathway in colon cancer.; Gastroenterology, 2010 PubMed Europe PMC Scholia* ... Transforming Growth Factor β Signaling in Colorectal Cancer Cells With Microsatellite Instability Despite Biallelic Mutations ...
DNA damage response curtails detrimental replication stress and chromosomal instability induced by the dietary carcinogen PhIP. ...
"Chromosomal Instability" by people in this website by year, and whether "Chromosomal Instability" was a major or minor topic of ... "Chromosomal Instability" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Alternative splicing of CHEK2 and codeletion with NF2 promote chromosomal instability in meningioma. Neoplasia. 2012 Jan; 14(1 ... EGFRvIII expression and PTEN loss synergistically induce chromosomal instability and glial tumors. Neuro Oncol. 2009 Feb; 11(1 ...
This type of chromosomal instability is by far the most frequent form of genetic instability among solid tumor cells and ... Prostate-specific membrane antigen associates with anaphase-promoting complex and induces chromosomal instability. Sigrid A. ... Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol 2001;3:433-8. ... 6E, arrow, and F), which provided further evidence for chromosomal instability (38). ...
Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability Message subject: (Your ...
Testing for Herpesvirus Infection Is Essential in Children with Chromosomal-Instability Syndromes. Petra Lankisch, Heiko Adler ... While active EBV replication may obviously end up in significant clinical problems in patients with chromosomal instability ... Cases of herpesvirus infection in children with chromosomal instability syndromes, diagnosed since 2006 at the Department of ... Testing for Herpesvirus Infection Is Essential in Children with Chromosomal-Instability Syndromes ...
Centrosome amplification drives chromosomal instability in breast tumor development. Proc Natl Acad Sci U S A 2002;99:1978-83. ... Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis. Gut 2008;57:941-50. ... Chromosomal instability detected by fluorescence in situ hybridization in Japanese breast cancer patients. Clin Chim Acta 2001; ... Paradoxical relationship between chromosomal instability and survival outcome in cancer. Cancer Res 2011;71:3447-52. ...
The chromosomal instability phenotype initiated by partial Bre1b knockdown (shBre1b1 cells grown without doxycycline) for 3 ... Deficiency in Mammalian Histone H2B Ubiquitin Ligase Bre1 (Rnf20/Rnf40) Leads to Replication Stress and Chromosomal Instability ... Deficiency in Mammalian Histone H2B Ubiquitin Ligase Bre1 (Rnf20/Rnf40) Leads to Replication Stress and Chromosomal Instability ... Deficiency in Mammalian Histone H2B Ubiquitin Ligase Bre1 (Rnf20/Rnf40) Leads to Replication Stress and Chromosomal Instability ...
Thus, chromosomal instability seen in Ink4a/Arf deficient tumors in vitro may be unrelated to the original phenotype of the ... However, after multiple passages chromosomal instability becomes apparent as evidenced by increasing tetraploidy and aneuploidy ... We found that chromosomal instability in Ink4a/Arf deficient MEFs developed with the same timing as seen in cell lines derived ... To further evaluate the effect of Ink4a/Arf-deficiency on chromosomal stability in vitro, we isolated Ink4a/Arf deficient ...
However, lamin A/C-deficient cells exhibit a phenotype of chromosomal numerical instability, though the mechanism was not ... Thompson SL, Bakhoum SF, Compton DA: Mechanisms of chromosomal instability. Curr Biol. 2010, 20: 285-295. 10.1016/j.cub.2010.01 ... Holland AJ, Cleveland DW: Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis. Nat Rev Mol Cell Biol. 2009 ... Nuclear envelope structural defects cause chromosomal numerical instability and aneuploidy in ovarian cancer. ...
  • It is clear that chromosomal instability can lead to aneuploidy, but whether the opposite is true has been much debated in the field of cancer biology. (pnas.org)
  • The concept that aneuploidy automatically triggers chromosomal instability has been propagated in the scientific literature in recent years. (pnas.org)
  • Here, we show that aneuploidy does not, on its own, lead to chromosomal instability, even when cells acquire chromosome alterations typical of cancer. (pnas.org)
  • In contrast, somatic aneuploidy, found mainly in neoplastic tissue, is attributed to continuous chromosomal instability. (pnas.org)
  • that is, whether aneuploidy per se causes chromosomal instability, for example, in patients with inborn aneuploidy. (pnas.org)
  • We have addressed this issue by quantifying the level of somatic mosaicism, a proxy marker of chromosomal instability, in patients with constitutional aneuploidy by precise background-filtered dual-color FISH. (pnas.org)
  • Our findings show that even though constitutional aneuploidy was in some cases associated with low-level somatic mosaicism, it was insufficient to generate the cancer-like levels expected if aneuploidy single-handedly triggered cancer-like chromosomal instability. (pnas.org)
  • 2014. "Chromosomal Instability, Aneuploidy, and Cancer. (harvard.edu)
  • However, after multiple passages chromosomal instability becomes apparent as evidenced by increasing tetraploidy and aneuploidy, and the concomitant loss of clonality. (spandidos-publications.com)
  • Herein, transduction of cyclin D1-/- mouse embryonic fibroblasts (MEFs) with the kinase dead KE mutant of cyclin D1 led to aneuploidy, abnormalities in mitotic spindle formation, autosome amplification, and chromosomal instability (CIN) by gene expression profiling. (jefferson.edu)
  • The aim of this thematic series was to bring together the latest research findings and conceptual developments in the field of chromosomal imbalances and cancer, publishing original research papers on the complex interplay of chromosomal instability and aneuploidy in cancerous and pre-cancerous lesions, and papers exploring potential translational aspects. (biomedcentral.com)
  • Furthermore, increased chromosomal aberrations, aneuploidy, and centrosome abnormalities were observed in the cyclin D1-rescued cells by spectral karyotyping and immunofluorescence. (jci.org)
  • One of theprimary reasons for this is that whole chromosomal abnormalities, or aneuploidy, are incredibly common incleavage-stage human embryos. (elsevier.com)
  • Although cellular fragmentation is closely linked with aneuploidy generation andmicronuclei formation, the source of these fragments and their precise chromosomal content is not welldefined. (elsevier.com)
  • By applying whole-genome next-generation sequencing (NGS) forcomprehensive chromosomal assessment, we will first determine the frequency of aneuploidy and sub-chromosomal errors during meiosis in individual mature rhesus oocytes and zygotes and potential correctionupon chromosome-induced polar body extrusion. (elsevier.com)
  • We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN). (nih.gov)
  • In vivo, Plk1 overexpression prevents the development of Kras-induced and Her2-induced mammary gland tumors, in the presence of increased rates of chromosome instability. (nih.gov)
  • Consistent molecular mechanisms responsible for the CIN + phenotype and hence means to target this pattern of genome instability in colorectal and other solid tumors remain poorly defined. (aacrjournals.org)
  • EGFRvIII expression and PTEN loss synergistically induce chromosomal instability and glial tumors. (umassmed.edu)
  • Thus, chromosomal instability seen in Ink4a/Arf deficient tumors in vitro may be unrelated to the original phenotype of the tumor in vivo. (spandidos-publications.com)
  • To better understand this seemingly contradictory relationship between CIN and cancer cell biological fitness and its relationship with clinical outcome, we applied the CIN70 expression signature, which correlates with DNA-based measures of structural chromosomal complexity and numerical CIN in vivo, to gene expression profiles of 2,125 breast tumors from 13 published cohorts. (dtu.dk)
  • Tumors with extreme CIN, defined as the highest quartile CIN70 score, were predominantly of the estrogen receptor negative (ER-), basal-like phenotype and displayed the highest chromosomal structural complexity and chromosomal numerical instability. (dtu.dk)
  • Stage 1, 2, 3 and 4 tumors did not differ significantly at the level of their CNA profiles precluding the conventional definition of a progression scheme based on increasing levels of genetic instability. (biomedcentral.com)
  • While tumors of the high risk group were characterized by frequent fractional CNAs, low risk tumors presented predominantly whole chromosomal arm CNAs. (biomedcentral.com)
  • However, they suggest that stage 2-3 CRC with elevated genetic instability and particularly profiles with fractional CNA represent a subset of aggressive tumors. (biomedcentral.com)
  • Chromosomal instability (CIN) as part of genomic instability is an inherent characteristic of most solid tumors and is also involved in breast cancer development. (figshare.com)
  • Cyclin D1 is overexpressed in many human tumors, and Casimiro and colleagues investigate its role in driving a transcriptional program that promotes chromosome instability. (jci.org)
  • In lactotroph tumors, genome instability, especially quantity of gains, significantly predicted recurrence independently of invasion and proliferation (p-value = 0.02, OR = 1.2). (biomedcentral.com)
  • Although CIMP is probably the cause of high-frequency microsatellite instability (MSI-H) sporadic CRCs, its role in microsatellite stable (MSS) tumors is debated. (elsevier.com)
  • The more common form of genomic instability in CRC is chromosomal instability (CIN), resulting in ongoing numerical and structural chromosomal aberrations in cancer cells, leading to intratumoral heterogeneity ( 2, 3 ). (aacrjournals.org)
  • In particular, they are preferential sites for chromosomal aberrations, viral DNA integration and are linked to the onset of oncogenesis and other disorders. (frontiersin.org)
  • Chromosomal aberrations and deoxyribonucleic acid single-strand breaks in adipose-derived stem cells during long-term expansion in vitro. (semanticscholar.org)
  • Well spread metaphases were scored for chromosomal aberrations (CA). (radioprotection.org)
  • Analysis of the spectrum of CA indicated chromatide type aberrations as the main chromosomal lesions for these experiments. (radioprotection.org)
  • The chromosome type aberrations were the main chromosomal lesions for noncontaminated and contaminated irradiated lymphocyte cultures, but shift to chromatide type aberrations was observed for CA spectrum of irradiated lymphocytes incubated with irradiated S. cerevisiae . (radioprotection.org)
  • The mutant cells also have a high level of spontaneous chromosomal aberrations and 3-fold elevated sister chromatid exchange. (elsevier.com)
  • The spontaneous chromosomal aberrations in XRCC9 cDNA transformants were almost fully corrected whereas sister chromatid exchanges were unchanged. (elsevier.com)
  • Chromosomal aberrations were detected in 2/18 patients (11 %) before allogeneic SCT, in 12/13 patients (92 %) after 3 months, in all patients after 12 months and in all patients in the retrospective group after allogeneic SCT. (biomedcentral.com)
  • Reciprocal translocations were the most common aberrations, but all other types of stable, structural chromosomal aberrations were also observed. (biomedcentral.com)
  • Ionizing radiation has the capacity to induce chromosomal aberrations in a variety of human tissues. (biomedcentral.com)
  • The goal of this study was to compare how accumulation of chromosomal aberrations in human papillomavirus (HPV)-infected cells correlates with the severity of cervical dysplastic lesions. (elsevier.com)
  • Genetic instability or changes in chromosome structure and numbers is an important facet of oncogenesis. (pnas.org)
  • The consequence of genetic instability can be an alteration in copy number of one or more genes, a change in gene expression, or a change in gene structure such that the protein sequence is altered ( 1 ). (pnas.org)
  • Genetic instability can result from changes in chromosome structure, through errors in DNA metabolism, repair, recombination, or other rearrangements of the DNA sequence ( 2 ), or from misregulation of the cell cycle, for example, uncoupling DNA replication from cell division ( 3 ) or centrosomal duplication from division ( 4 ). (pnas.org)
  • Abnormalities in the chromosomal segregational apparatus are also likely to play an important role in genetic instability. (pnas.org)
  • One of the most striking manifestations of genetic instability in cancer cells is the variation observed in the karyotypes of different cells, even within the same tumor. (pnas.org)
  • Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. (nih.gov)
  • Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. (mdpi.com)
  • Earlier studies have shown an association between telomere shortening and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and cancer. (mdpi.com)
  • Clearly, genetic instability and clonal evolution are driving forces for leukemic transformation. (mdpi.com)
  • The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. (wikipathways.org)
  • Tumor-initiating cells (TIC) that are responsible for tumorigenesis are a source of functional cellular heterogeneity, whereas chromosomal instability (CIN) is a source of karyotypic genetic diversity. (aacrjournals.org)
  • It remains presently unclear whether disease progression in colorectal carcinoma (CRC), from early, to invasive and metastatic forms, is associated to a gradual increase in genetic instability and to a scheme of sequentially occurring Copy Number Alterations (CNAs). (biomedcentral.com)
  • In this work we set to determine the existence of such links between CRC progression and genetic instability and searched for associations with patient outcome. (biomedcentral.com)
  • Our data show that CRC disease progression from stage 1 to stage 4 is not paralleled by increased levels of genetic instability. (biomedcentral.com)
  • It is generally agreed that tumor progression occurs according to a scheme of gradual accumulation of genetic anomalies and that genetic instability is highest in most aggressive and metastatic forms of the disease. (biomedcentral.com)
  • Instead, adaptive mutation and amplification are parallel routes of inducible genetic instability allowing rapid evolution under stress, and escape from growth inhibition. (butler.edu)
  • Addressing these knowledge gaps regarding correlations among tissue-specific TLs, the relationship between TL and chromosomal instability, and tissue-specific genetic effects on TL is a critical step towards elucidating the role of TL in the etiology of cancer and other common diseases. (grantome.com)
  • Using a combination of NGS and non-invasive time-lapseimaging to monitor early cleavage divisions and cellular fragmentation dynamics, we will then evaluate theincidence of mitotic chromosomal mis-segregation up to the ~8-cell stage and reconstruct all whole and sub-chromosomal errors in each rhesus embryo by analyzing the genetic content of both single cells andfragments. (elsevier.com)
  • Hence, introgressions and chromosomal rearrangements appear to have made a major contribution to genetic diversity in cultivar collections. (grassroots.tools)
  • These findings suggest that CIN and CIMP represent 2 independent and inversely related mechanisms of genetic and epigenetic instability in sporadic CRCs and confirm that MSI cancers arise as a consequence of CIMP. (elsevier.com)
  • Jaspers NG, Taalman RD, Baan C. Patients with an inherited syndrome characterized by immunodeficiency, microcephaly, and chromosomal instability: genetic relationship to ataxia telangiectasia. (medscape.com)
  • These data implicate multiple molecular and genetic pathways leading to different manifestations of genomic instability in GM10115 cells surviving exposure to DNA-damaging agents. (elsevier.com)
  • Correlation of 3q26 and 8q24 aneusomy with concurrent HPV infection may thus serve as a biomarker of genetic instability in HPV-infected cells. (elsevier.com)
  • Spontaneous chromosome missegregation events in aneuploid cells promote chromosomal instability (CIN) that may contribute to the acquisition of multidrug resistance in vitro and heighten risk for tumor relapse in animal models. (aacrjournals.org)
  • Dysfunctional DNA damage and mitotic spindle checkpoints resulting from these interactions may promote chromosomal instability and leave the hepatocyte unable to control DNA damage caused by oxidative stress mediated by HCV proteins, alcohol, and immune-mediated inflammation. (mysciencework.com)
  • The less common pattern is microsatellite instability (MIN) caused by a deficiency in the mismatch repair apparatus. (aacrjournals.org)
  • The second, known as microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. (wikipathways.org)
  • Transforming Growth Factor β Signaling in Colorectal Cancer Cells With Microsatellite Instability Despite Biallelic Mutations in TGFBR2. (wikipathways.org)
  • Survival in stage II/III colorectal cancer is independently predicted by chromosomal and microsatellite instability, but not by specific driver mutations. (ox.ac.uk)
  • OBJECTIVES: Microsatellite instability (MSI) is an established marker of good prognosis in colorectal cancer (CRC). (ox.ac.uk)
  • Lastly, we will assess the potential contribution of meiotic chromosomal mis-segregation to mitoticerrors and subsequent development by performing polar body biopsy on zygotes, allowing the embryo toproceed until the ~8-cell stage, and distinguishing meiotic versus mitotic errors based on chromosomalmosaicism, fragmentation timing, and microsatellite analysis. (elsevier.com)
  • We assessed other molecular events including loss of heterozygosity (LOH) in 2p, 5q, 17q, and 18q, the CpG island methylation phenotype (CIMP), and microsatellite instability (MSI). (core.ac.uk)
  • Ulcerative colitis (UC), a chronic inflammatory condition associated with a predisposition to colon cancer, is frequently characterized by DNA damage in the form of microsatellite instability (MSI). (jci.org)
  • Oral squamous cell carcinomas are characterized by complex, often near-triploid karyotypes with structural and numerical variations superimposed on the initial clonal chromosomal alterations. (pnas.org)
  • Vajen B, Thomay K, Schlegelberger B. Induction of Chromosomal Instability via Telomere Dysfunction and Epigenetic Alterations in Myeloid Neoplasia. (mdpi.com)
  • To address these gaps, we propose to assess the cross-tissue correlations among telomere length measurements taken across many cancer-prone tissues and determine if these measures are correlated with chromosomal instability as measured by chromosomal alterations detected within the tissue samples. (grantome.com)
  • High CIN70 scores were significantly related to increased chromosomal alterations in TCGA cervical cancer patients, including a higher percentage of genome altered and a higher number of copy number alterations. (beds.ac.uk)
  • CIN70 score was found to be significantly associated with chromosomal alterations and para-aortic distant relapse in patients. (beds.ac.uk)
  • A high frequency of Chromosomal alterations was found in the exposed group in comparison with those observed in the unexposed group. (urosario.edu.co)
  • Numerical chromosomal alterations, fragilities and chromosomal breaks showed significant differences between exposed and unexposed groups. (urosario.edu.co)
  • The high frequency of both Chromosomal Alterations and DNA Damage Index observed in this study indicates an urgent need of intervention not only to prevent the increased risk of developing cancer but also to the application of strict health control and motivation to the use of appropriate protecting devices during work. (urosario.edu.co)
  • We used immunohistochemistry combined with classical cytogenetic analysis and spectral karyotyping to investigate the chromosomal segregation defects in cultured oral squamous cell carcinoma cells. (pnas.org)
  • These results indicate that some of the chromosomal instability observed within these cancer cells might be the result of cytoskeletal defects and breakage-fusion-bridge cycles. (pnas.org)
  • During mitotic division, we observed multiple segregational defects, including multipolar spindles, lagging chromosomes, and anaphase bridges, leading to chromosomal breakage at telophase into centric and acentric micronuclei. (pnas.org)
  • 2000) The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. (springer.com)
  • We show here that re‐introduction of one copy of the Terc gene in these mice via Terc +/− × Terc −/− crosses is sufficient to elongate critically short telomeres, rescue chromosomal instability and prevent severe proliferative defects in these mice. (embopress.org)
  • phospho-HH3-Ser 10 ) to functional outcomes (e.g., chromosomal congression defects). (aacrjournals.org)
  • DNA double-strand break and chromosomal rejoining defects with misrejoining in Nijmegen breakage syndrome cells. (medscape.com)
  • Lymph node metastasis in oral cancer is strongly associated with chromosomal instability and DNA repair defects. (cdc.gov)
  • Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. (nih.gov)
  • Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. (nih.gov)
  • Chromosomal instability produces cytosolic micronuclei that rupture and activate a viral response pathway, driving metastasis. (sciencemag.org)
  • abstract = "Chromosomal destabilization is one end point of the more general phenomenon of genomic instability. (elsevier.com)
  • Despite the numerous and diverse abnormalities, classical cytogenetic analyses of OSCC cells have revealed several consistent chromosomal changes, such as breakpoints at bands 1p11-1p13, 3p14, and 11q13 ( 6 ) and amplification of band 11q13 ( 7 , 8 ). (pnas.org)
  • Certain constellations of findings might suggest specific chromosomal syndromes, and ambiguous genitalia might be associated with sex chromosome abnormalities. (alpfmedical.info)
  • indeed, among spontaneous miscarriages in humans with chromosomal abnormalities, triploidy and tetraploidy are responsible for approximately 20%, and this corresponds to 10% of total miscarriages (Carr et al. (biologists.org)
  • We found no influence of incubation with irradiated yeast cells on the average level of chromosomal instability in X-ray exposed lymphocytes. (radioprotection.org)
  • The level of chromosomal instability in CCC as defined by the extent of DNA copy number changes is similar to those previously reported in low-grade ovarian serous carcinoma but much less than those in high-grade serous carcinoma. (aacrjournals.org)
  • While active EBV replication may obviously end up in significant clinical problems in patients with chromosomal instability syndromes, other herpesvirus infections may also become clinically relevant and should not be overlooked in the diagnostic workup. (asm.org)
  • Pericentromeric demethylation and chromosomal instability induced by chemicals - Descarga este documento en PDF. (duhnnae.com)
  • When study lead author Neil Ganem, PhD, of Dana-Farber used newly developed microscope equipment to watch living cancer cells for a week or more, he found that not only were such abnormal divisions quite rare, but the resulting daughter cells were so discombobulated by their chromosomal quirks, they generally survived for only a few days "" far too briefly to deliver abnormal chromosome content to a tumor. (redorbit.com)
  • The way that extra centrosomes do cause chromosome instability, Ganem and his colleagues have discovered, is by setting up a tug-of-war for chromosomes that are eventually caught between newly forming daughter cells of a dividing cancer cell. (redorbit.com)
  • Chromosome instability is a hallmark of most cancer cells, arising when chromosomes are missegregated into daughter cells during division," said Ganem, who led the study with senior author David Pellman, MD, and co-author Susana Godinho, PhD, of Dana-Farber. (redorbit.com)
  • Another common finding in cancer cells is chromosomal instability, a condition in which cells change their chromosomal content at a high rate. (pnas.org)
  • In contrast to previous studies that used less precise methods, we find that constitutional trisomy, even for large chromosomes that are often trisomic in cancer, does not confer a significantly elevated rate of somatic chromosomal mosaicism in individual cases. (pnas.org)
  • Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. (nih.gov)
  • Confirming the association of CIN rather than ploidy status with multidrug resistance, tetraploid isogenic cells that had arisen from diploid cell lines displayed lower drug sensitivity than their diploid parental cells only with increasing chromosomal heterogeneity and isogenic cell line models of CIN + displayed multidrug resistance relative to their CIN − parental cancer cell line derivatives. (aacrjournals.org)
  • Colorectal cancer (CRC) is associated with at least 2 distinct patterns of genomic instability ( 1 ). (aacrjournals.org)
  • Clarifying the mechanisms underlying CFS instability during tumorigenesis will further advance our understanding of cancer etiology and shed new light on cancer treatment. (frontiersin.org)
  • Chromosomal instability (CIN) is a characteristic feature of cancer. (mdpi.com)
  • The chromosomal instability pathway in colon cancer. (wikipathways.org)
  • Altered mitotic spindle assembly checkpoint function, centrosome duplication, kinetochore function, and microtubule stability have been implicated in chromosome missegregation and the ensuing pattern of chromosomal instability (CIN) in cancer model systems ( 1 ). (aacrjournals.org)
  • Chromosomal instability (CIN) is associated with poor prognosis in human cancer. (dtu.dk)
  • Assessment of a limited number of chromosomal structural instabilities by use of massive parallel sequencing of cfDNA was sufficient to distinguish between prostate cancer and controls. (aaccjnls.org)
  • Our interest in prostate cancer is based on the recent discoveries that almost all cancer types exhibit chromosomal structural instability, through either progressive evolution or catastrophic genomic events ( 3 ). (aaccjnls.org)
  • Considering cancer patients treated with partial body irradiation as a relevant group at risk of developing a second cancer, research has been carried out to quantify chromosomal instability (ChI) occurring in their lymphocytes. (radioprotection.org)
  • Tumor suppressors, chromosomal instability, and hepatitis C virus-associated liver cancer. (mysciencework.com)
  • The mechanisms by which it causes cancer are unclear, but chronic immune-mediated inflammation and associated oxidative chromosomal DNA damage probably play a role. (mysciencework.com)
  • Chromosomal imbalances have been known as common features of cancer genomes for a long time. (biomedcentral.com)
  • Chromosomal instability - as a process leading to abnormal chromosome content and heterogeneity - has been widely researched and increasingly referred to as driving force behind malignant transformation and defining factor for cancer evolution. (biomedcentral.com)
  • The unifying research aim of the department is the understanding of genomic instability in human cancer in order to tailor therapies for cancer patients. (dana-farber.org)
  • Across a diverse panel of breast cell lines, CENP-E inhibition by PF-2771 selectively inhibits proliferation of basal breast cancer cell lines relative to premalignant ones and its response correlates with the degree of chromosomal instability. (aacrjournals.org)
  • AURKA overexpression is observed in various cancers including colon cancer, and a link between AURKA and chromosomal instability (CIN) has been proposed. (core.ac.uk)
  • These findings demonstrate that chromosomal instability plays an important role in cervical cancer, and is significantly associated with patient outcome. (beds.ac.uk)
  • IMSEAR at SEARO: Chromosomal instability and cancer: An insight into the rhythm of life. (who.int)
  • The recent successes of CDK inhibitors in the clinic, combined with the potential for structure-based routes to the development of non-ATP-competitive CDK inhibitors, and evidence that CDK inhibitors may have use in suppressing chromosomal instability and in synthetic lethal drug combinations inspire optimism that CDK inhibitors will become important weapons in the fight against cancer. (aspetjournals.org)
  • Chromosomal changes are frequent in cancer and MSI has been clearly documented as a result of mutations in mismatch repair enzymes in the hereditary nonpolyposis colon cancer syndrome. (jci.org)
  • Telomere dysfunction plays a crucial role in initiating or sustaining genomic instability, which is a major step in cancer progression. (wikipedia.org)
  • Chromosomal instability (CIN) is a hallmark of many tumours and correlates with the presence of extra centrosomes. (nih.gov)
  • Kinase-independent role of cyclin D1 in chromosomal instability and mammary tumorigenesis. (jefferson.edu)
  • We conclude that the CDK-activating function of cyclin D1 is not necessary to induce either chromosomal instability or mammary tumorigenesis. (jefferson.edu)
  • These data suggest that cyclin D1 contributes to CIN and tumorigenesis by directly regulating a transcriptional program that governs chromosomal stability. (jci.org)
  • Acting in multiple central processes like double-strand break repair, centrosome replication, and checkpoint control, BRCA1 participates in maintaining genomic integrity and protects the cell against genomic instability. (figshare.com)
  • Premature activation of APC would provide less time for proper chromosome attachment and alignment and would thus reduce the fidelity of chromosomal segregation into daughter cells. (aacrjournals.org)
  • These findings led to suggestions that APC acts in chromosomal segregation and that APC inactivation leads to chromosomal instability (CIN). (ox.ac.uk)
  • Moreover, cancerous cells frequently contain multiple centrosomes [microtubule-organizing centers (MTOCs) (Box 1) that are required for proper chromosome segregation], which can lead to aberrant mitosis and errors in chromosomal segregation. (biologists.org)
  • The problem of delayed genomic instability occurring in human cells in vivo has recently come to prominence as an important mechanism in radiation carcinogenesis. (radioprotection.org)
  • This work serves as a precedent for the study of the mechanisms responsible for the degradation of essential mitotic proteins to prevent chromosomal instability. (brightsurf.com)
  • Adaptive amplification, an inducible chromosomal instability mechanism" by P. J. Hastings, H. K. Bull et al. (butler.edu)
  • These correlations may he explained by chromosomal destabilization, which can mediate gene amplification and can result in cellular lethality. (elsevier.com)
  • Kinase-independent role of cyclin D1 in chromosomal instability and ma" by Mathew C Casimiro, Gabriele Disante et al. (jefferson.edu)
  • show that in contrast to Cyclin D1-/- cells (left), those overexpressing Cyclin D (right) develop multiple centrosomes and abnormal spindle architecture, resulting in chromosomal instability. (jci.org)
  • Here, we used genome-wide ChIP sequencing and found that the DNA-bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. (jci.org)
  • However, some genomic regions can raise specific problems for the replication machinery, leading to chromosome breakage and genome instability. (frontiersin.org)
  • To conclude, CGH array analysis showed genome instability was dependent on PitNET type. (biomedcentral.com)
  • In contrast, CIN + CRC cell lines are aneuploid and display a higher frequency of chromosomal missegregation errors during each mitosis relative to diploid cells ( 2 ). (aacrjournals.org)
  • Heavy charged particles are very effective at producing chromosomal exchanges with RBE values exceeding 30 in interphase (as visualized using premature chromosome condensation) and 10 at the post-irradiation mitosis for energetic iron (Fe) ions. (wikipedia.org)
  • It is tempting to speculate that the higher genomic instability is related to cellular aging in adult RSCs. (arvojournals.org)
  • Ataxia-telangiectasia-like disorder (ATLD) is similar to the A-T in that patients show progressive cerebellar ataxia, however they do not show telangiectasias, and show normal immunoglobulin levels, later onset disease and a milder clinical course compared to A-T. At the cellular level, there is chromosomal instability, increased sensitivity to ionizing radiation, defective induction of stress-activated signal transduction pathways, and radioresistant DNA synthesis (Taylor et al. (preventiongenetics.com)
  • Scientists led by ICREA researcher Dr. Marco Milán at IRB Barcelona have revealed the link between chromosomal instability and cellular senescence. (news-medical.net)
  • In the multipolar spindles, the poles demonstrated different levels of chromosomal capture and alignment, indicating functional differences between the poles. (pnas.org)
  • Thus, we would like to call attention to the existence of more literature on the investigation of herpesvirus infection in children with chromosomal instability syndromes (e.g. (asm.org)
  • D'Andrea's focus is the molecular pathogenesis of the human chromosomal instability syndromes: Fanconi anemia (FA), ataxia-telangiectasia, and Bloom syndrome. (dana-farber.org)
  • MdmX regulates transformation and chromosomal stability in p53-deficient cells. (umassmed.edu)
  • To further evaluate the effect of Ink4a/Arf-deficiency on chromosomal stability in vitro, we isolated Ink4a/Arf deficient primary murine embryonic fibroblasts (MEFs), serially passaged them, and analyzed their chromosomal stability by spectral karyotyping (a 24-color chromosome paint-FISH technique). (spandidos-publications.com)
  • The incubation with nonirradiated yeast cells had no effect on lymphocytes chromosomal stability. (radioprotection.org)
  • In contrast, Terc +/− progeny showed all chromosomes with detectable telomeres, and did not show chromosomal instability or premature aging. (embopress.org)
  • Most dicentric chromosomes are known to form through chromosomal inversions, which are rotations in regions of a chromosome due to chromosomal breakages or intra-chromosomal recombinations. (wikipedia.org)
  • The resulting dicentric chromosomes are highly unstable, giving rise to chromosomal translocations, deletions and amplifications, such as the Robertsonian translocation. (wikipedia.org)
  • CFSs are chromosomal regions that are stable under normal conditions but display an increased rate of breakage under replication stress. (frontiersin.org)
  • DNA damage response curtails detrimental replication stress and chromosomal instability induced by the dietary carcinogen PhIP. (sigmaaldrich.com)
  • Combined with a previously reported defect in homologous recombination, generation of R-loops is a likely initiator of replication stress and genomic instability in Bre1-deficient cells. (aacrjournals.org)
  • Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, which cooperate in the FA/BRCA pathway. (encyclopedia.pub)
  • The aneuploid index was calculated as the sum of all the consistent chromosomal gains or losses present in the karyotype. (hindawi.com)
  • We have begun to investigate the source of chromosomal instability in cultured cells derived from human OSCC. (pnas.org)
  • According to Pellman, chromosomal instability, it turns out, "is actually a side effect of the cells' ability to cluster their excess centrosomes. (redorbit.com)
  • This particular morphology represents a potential new biomarker for the identification of cells with chromosomal instability. (brightsurf.com)
  • In addition, these cells exhibited a wide range of structural chromosomal changes that included multiple breakpoints within the same chromosome. (asm.org)
  • Misregulation of Scm3p/HJURP causes chromosome instability in Saccharomyces cerevisiae and human cells. (umassmed.edu)
  • We track the evolution of genomic instability in Bre1-deficient cells from replication-associated double-strand breaks (DSB) to specific genomic rearrangements that explain a rapid increase in DNA content and trigger breakage-fusion-bridge cycles. (aacrjournals.org)
  • Our data showed that silibinin inhibited expression of FAT10, TI-induced chromosome instability (CIN) as well as sensitizes cells to TI-induced apoptosis. (biologists.org)
  • Chromosomal instability of murine adipose tissue-derived mesenchymal stem cells in long-term culture and development of cloned embryos. (semanticscholar.org)
  • Chromosomal instability in bystander human lymphocytes incubated with irradiated yeast cells. (radioprotection.org)
  • Thompson, Larry H. / The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells . (elsevier.com)
  • However, these associations are difficult to interpret, in part because it is not clear (1) how well telomere lengh in peripheral blood cells reflects telomere length in the tissues most relevant to disease and (2) if tissue-specific telomere length actually reflects levels of within-tissue chromosomal instabilit. (grantome.com)
  • We previously established that chromosomal instability can manifest in clones derived from single progenitor cells several generations after X-irradiation. (elsevier.com)
  • The average number of double-positive cells increased from two cells in patients with a cytological interpretation of atypical squamous cells of undetermined significance to 22 cells in low-grade squamous intraepithelial lesion and 99 cells in high-grade squamous intraepithelial lesion, reflecting an accumulation of chromosomal abnormality with disease progression. (elsevier.com)
  • In fact, only a small fraction of the initial damage is transduction of late chromosomal damage has also been measured in the progeny of human lymphocytes that were exposed with much higher frequency in the progeny of cells that were exposed to heavy ions compared to gamma rays. (wikipedia.org)
  • Genomic instability has been observed both in vitro and in vivo in the progeny of cells that are irradiated with heavy ions in several model systems. (wikipedia.org)
  • The majority of MSS CRCs demonstrate chromosomal instability (CIN) with frequent loss of heterozygosity (LOH) at key tumor suppressor genes. (elsevier.com)
  • For this, we have crossed these mice with Terc +/− mice and analyzed telomere length, chromosomal instability and premature aging of the progeny. (embopress.org)
  • A mechanism linking extra centrosomes to chromosomal instability. (nih.gov)
  • Extreme chromosome 17 copy number instability is a prognostic factor in patients with gastroesophageal adenocarcinoma: A retrospective cohort study. (umassmed.edu)
  • To this aim we analyzed a set of 162 Chromosomal Instable (CIN) CRCs comprising 131 primary carcinomas evenly distributed through stage 1 to 4, 31 metastases and 14 adenomas by array-CGH. (biomedcentral.com)
  • We, also, asked whether the level of genomic instability was correlated to disease outcome in stage 2 and 3 CRCs. (biomedcentral.com)
  • We propose that genomic instability triggered by Bre1 deficiency may be an important early step that precedes acquisition of an invasive phenotype, as we find decreased levels of BRE1A/B and dimethylated H3K79 in testicular seminoma and in the premalignant lesion in situ carcinoma. (aacrjournals.org)
  • These clones were then subjected to a series of assays to determine whether chromosomal instability is associated with a general 'mutator phenotype' and whether it modulates other end points of genomic instability. (elsevier.com)
  • Until now, the only biomarker to determine chromosomal instability was the micronucleus. (brightsurf.com)
  • Analysis of chromosomal instability in human colorectal adenomas with two mutational hits at APC. (ox.ac.uk)
  • found that rearrangements involving telomere regions are associated with chromosomal instability in human fibroblasts that occur many generations after exposure to accelerated heavy ions. (wikipedia.org)
  • The mechanisms responsible for CFS instability are hotly debated but different models all point to their inability to complete replication. (frontiersin.org)
  • Two major mechanisms of genomic instability have been identified in sporadic CRC progression. (wikipathways.org)
  • Our long-term data suggest that this damage increases with time, possibly due to in vivo radiation-induced chromosomal instability. (biomedcentral.com)