Chromosomal Instability: An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.Aneuploidy: 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).Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.Joint Instability: 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.Microsatellite Instability: 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.In Situ Hybridization, Fluorescence: 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.Centrosome: 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).Chromosome Fragility: Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.Telomere: 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.Chromosome Breakage: A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.Mitosis: 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.Karyotyping: Mapping of the KARYOTYPE of a cell.Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.DNA Damage: 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.Fanconi Anemia: 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)Microsatellite Repeats: 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).DNA Repair: 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.Nijmegen Breakage Syndrome: 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.Ploidies: The degree of replication of the chromosome set in the karyotype.Polyploidy: The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.Cell Cycle Proteins: 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.Loss of Heterozygosity: 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 Transformation, Neoplastic: 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.Mutation: 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.Aurora Kinase A: 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.Colorectal Neoplasms: 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.Chromosomes: 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)Bloom Syndrome: 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.Chromosomes, Human: 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.Sister Chromatid Exchange: 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.Micronuclei, Chromosome-Defective: 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.Nuclear Proteins: 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.Aurora Kinases: 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, Neoplasm: DNA present in neoplastic tissue.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Chromosome Fragile Sites: 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 Proteins: 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.Tumor Suppressor Protein p53: 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.Spindle Apparatus: 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.Ataxia Telangiectasia: 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).Telomerase: An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.Neoplasms: 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.DNA-Binding Proteins: 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.Spectral Karyotyping: 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.Cytogenetic Analysis: 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.Fanconi Anemia Complementation Group G Protein: 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.Diploidy: The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.Telomere Shortening: 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.Fanconi Anemia Complementation Group Proteins: 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.Chromosome Disorders: 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)RecQ Helicases: 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.Centromere: 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.Micronucleus Tests: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Radiation, Ionizing: 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.Metaphase: 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.DNA Breaks, Double-Stranded: Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Ataxia Telangiectasia Mutated Proteins: 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.Microcephaly: 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.)M Phase Cell Cycle Checkpoints: The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.Gene Dosage: 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.Anaphase: The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.Comparative Genomic Hybridization: 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.Chromosomes, Human, Pair 4: A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.Fanconi Anemia Complementation Group C Protein: 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.Fanconi Anemia Complementation Group A 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.Mitomycin: 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.Cell Cycle: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.X-Rays: 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.Cytokinesis: The process by which the CYTOPLASM of a cell is divided.DNA Replication: The process by which a DNA molecule is duplicated.Recombination, Genetic: 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.Microtubules: 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.Hypoxanthine Phosphoribosyltransferase: 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.F-Box Proteins: 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.Fanconi Anemia Complementation Group F Protein: 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.Neoplasm Proteins: 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.Allelic Imbalance: A situation where one member (allele) of a gene pair is lost (LOSS OF HETEROZYGOSITY) or amplified.Gene Amplification: 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.Translocation, Genetic: A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.Gene Deletion: 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.Nucleic Acid Hybridization: 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)Rad51 Recombinase: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.Chromosomes, Human, Pair 17: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.Gonadal Disorders: Pathological processes of the OVARIES or the TESTES.Tetraploidy: The presence of four sets of chromosomes. It is associated with ABNORMALITIES, MULTIPLE; and MISCARRAGES.DNA Helicases: 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: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Bystander Effect: 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.Chromosomes, Human, Pair 7: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Gonadal Dysgenesis, 46,XX: 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.Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.Mosaicism: 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.Radiation Tolerance: 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.DNA: 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).Models, Biological: 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.BRCA2 Protein: 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)Chromosomes, Human, Pair 20: A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.Lymphocytes: 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.Tumor Cells, Cultured: 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.DNA Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.Cells, Cultured: 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.Antigens, Nuclear: Immunologically detectable substances found in the CELL NUCLEUS.Tumor Suppressor Proteins: 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.Hybrid Cells: 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.Colonic Neoplasms: Tumors or cancer of the COLON.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Telomeric Repeat Binding Protein 1: 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.Cell Aging: 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.Polymerase Chain Reaction: 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, cdc: 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).Precancerous Conditions: Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)Chromosome Deletion: Actual loss of portion of a chromosome.Fanconi Anemia Complementation Group D2 Protein: 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.Gamma Rays: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.CpG Islands: 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: 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.Adaptor Proteins, Signal Transducing: 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 enzymesTelomeric Repeat Binding Protein 2: 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.Syndrome: A characteristic symptom complex.Molecular Sequence Data: 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: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Cell Line, Transformed: 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.Prognosis: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Breast Neoplasms: Tumors or cancer of the human BREAST.Mitotic Index: An expression of the number of mitoses found in a stated number of cells.Models, Genetic: 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.DNA Sequence, Unstable: 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.Adenomatous Polyposis Coli Protein: A negative regulator of beta-catenin signaling which is mutant in ADENOMATOUS POLYPOSIS COLI and GARDNER SYNDROME.Genes, ras: 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.Disease Progression: 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.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Cyclin B: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Mice, Knockout: 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.Adenoma: A benign epithelial tumor with a glandular organization.G2 Phase: 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.Epigenesis, Genetic: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.JC Virus: 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.Chromosomes, Human, Pair 18: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.Genes, APC: 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.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.Cell Nucleus: 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)Apoptosis: 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, Neoplasm: Genes whose abnormal expression, or MUTATION are associated with the development, growth, or progression of NEOPLASMS.Cell Survival: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Base Pair Mismatch: 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).Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Cyclin E: 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.
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 ...
Principal Investigator:YAMASHITA Takayuki, Project Period (FY):1999 - 2000, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Hematology
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
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
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 ...
CONICET Digital, el repositorio institucional del CONICET, un servicio gratuito para acceder a la producción científico-tecnológica de investigadores, becarios y demás personal del CONICET.
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.. ...
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 ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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. ...
BACKGROUND: Telomeres are repetitive DNA sequences and associated proteins that cap the ends of chromosomes. Functional telomeres protect genetic information and maintain chromosomal stability. Critically short telomeres ...
BACKGROUND: Telomeres are repetitive DNA sequences and associated proteins that cap the ends of chromosomes. Functional telomeres protect genetic information and maintain chromosomal stability. Critically short telomeres ...
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.
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, ...
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. ...
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.
In the present study, we found that the centrosomes in nearly all pancreatic ductal carcinomas displayed structural abnormalities, such as an increase in their number and size, and an irregular distribution. Quantitative analysis demonstrated a significant difference in centrosome number between normal and cancer cells. In addition, double-labeled immunofluorescence analysis of MIA PaCa-2 pancreatic cancer cells suggest that these aberrant centrosomes contribute to the assembly of multipolar spindles, which may result in the improper segregation of chromosomes during mitosis. These results are consistent with previous studies describing centrosome abnormalities in human malignant tumors of the breast, prostate, brain, lung, and colon (10 , 11) . To our knowledge, however, this is the first report to demonstrate centrosome abnormalities in pancreatic carcinoma.. The centrosome plays a key role in the organization of cytoplasmic microtubules, in the determination of cell polarity, and in the ...
Cells have intrinsic mechanisms that facilitate centrosome clustering (Godinho and Pellman, 2014). Thus, it is thought that cells are unlikely to require adaptation to centrosome amplification, which is further supported by the fact that most cancer cell lines with extra centrosomes are able to cluster centrosomes efficiently (Ring et al., 1982; Quintyne et al., 2005; Kwon et al., 2008; Ganem et al., 2009). However, our findings challenge this idea and indicate that at least in epithelial tumors, cancer cells need to adapt to efficiently proliferate in the presence of supernumerary centrosomes. We demonstrate that induction of centrosome amplification in a panel of nontransformed cell lines reveals intrinsic differences in clustering ability, with epithelial cells displaying an inefficient process. These differences are not caused by centrosome inactivation, as previously shown in Drosophila cells with extra centrosomes (Sabino et al., 2015), highlighting that the prevalence of mechanisms that ...
Neoplastic cells are genetically unstable. Strategies that target pathways affecting genome instability can be exploited to disrupt tumor cell growth potentially with limited consequences to normal cells. Chromosomal instability (CIN) is one type of genome instability characterized by mitotic defects that increase the rate of chromosome mis-segregation. CIN is frequently caused by extra centrosomes that transiently disrupt normal bipolar spindle geometry needed for accurate chromosome segregation. Tumor cells survive with extra centrosomes because of biochemical pathways that cluster centrosomes and promote chromosome segregation on bipolar spindles. Recent work shows that targeted inhibition of these pathways prevents centrosome clustering and forces chromosomes to segregate to multiple daughter cells, an event triggering apoptosis that we refer to as anaphase catastrophe. Anaphase catastrophe specifically kills tumor cells with more than two centrosomes. This death program can occur after ...
3197 Cyclin E, a regulatory subunit of CDK2 has key S phase promoting functions in normal cells. Cyclin E is often overexpressed and present in low molecular weight (LMW) isoforms in malignant cells and such deregulation is associated with aggressive disease and poor outcome. Stable overespression of LMW cyclin E in breast cancer cells promotes chromosome instability in breast cancer cells. Examination of human cancer tissues and cultured cells has revealed a significant correlation between loss and/or mutation of tumor suppressor p53 and occurrence of centrosome amplification. We hypothetized that cyclin E LMW overexpression together with p53 depletion, cooperate to efficiently induce spindles abnormalities and centrosome amplification leading to chromosomal instability. To test this hypothesis we generated a model system composed of MCF-7 cells, which inducibly overexpress the LMW cyclin E protein under control of tetracycline-inducible promoter. Short-term induction of LMW of cylin E for 24 ...
Genetic and Molecular Basis of Chromosome Instability. Funded by: Canadian Cancer Society Research Institute, Ontario Government Early Research Award, NSERC Discovery Award.. Scientists have found chromosome gain or loss in nearly all major human tumour types. Dr. Baetzs current research project involves developing and implementing yeast chemical and functional genomic screens in order to identify networks of proteins required for chromosome stability in S. cerevisiae. Once the proteins that are required for chromosome stability are identified, she and her research team uses traditional methods drawn from biochemistry and molecular biology to reveal the molecular mechanisms used by these proteins to prevent chromosome loss. Considering the conservation between yeast and human processes governing chromosome segregation, the Baetz laboratorys research with yeast will be of directly relevance to human cancer biology, and will provide new insights into the molecular mechanism of chromosomal ...
Tumors are dynamic organs that evolve during disease progression with genetic, epigenetic, and environmental differences among tumor cells serving as the foundation for selection and evolution in tumors. 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. However, the extent that CIN contributes to TIC genetic diversity and its relationship to TIC function remains unclear. Here, we demonstrate that glioblastoma TICs display CIN with lagging chromosomes at anaphase and extensive nonclonal chromosome copy-number variations. Elevating the basal chromosome missegregation rate in TICs decreases both proliferation and the stem-like phenotype of TICs in vitro. Consequently, tumor formation is abolished in an orthotopic mouse model. These results demonstrate that TICs generate genetic heterogeneity within tumors, but that TIC function is impaired if the ...
We are interested in understanding the structure, function and evolution of ribonucleoprotein (RNP) complexes in cells. Our attention currently focuses on the telomerase RNP enzyme, a unique reverse transcriptase essential for maintaining telomere length in most eukaryotes. Telomeres act as caps at the ends of chromosomes, and are required for chromosome stability.. Telomerase elongates telomere length by adding telomeric repeats to chromosome ends to counterbalance the natural shortening that occurs during DNA replication. Because of its role in chromosome stability, telomerase regulation is a critical step in tumorigenesis and aging. To maintain chromosome stability and infinite growth, telomerase is activated in immortal cells such as stem cells, germ line as well as 90% of human tumors. Moreover, patients with dyskeratosis congenita, a disease of premature aging, carry a mutation in the telomerase RNA (TR) or the telomerase reverse transcriptase protein (TERT) genes. Elucidation of the ...
Our research program is focused on the important basic question of how chromosomes are segregated during cell division to ensure the complete and accurate inheritance of the genome. Chromosome instability is a hallmark of cancer and can drive tumorigenesis. Therefore, how centromere specification is controlled is a basic biological question with great therapeutic potential. Centromeres are specified by the incorporation of a histone variant CENP-A, and stable inheritance of this locus is control...[Read full text]Our research program is focused on the important basic question of how chromosomes are segregated during cell division to ensure the complete and accurate inheritance of the genome. Chromosome instability is a hallmark of cancer and can drive tumorigenesis. Therefore, how centromere specification is controlled is a basic biological question with great therapeutic potential. Centromeres are specified by the incorporation of a histone variant CENP-A, and stable inheritance of this locus ...
Changes in the genome that allow uncontrolled cell proliferation or cell immortality are responsible for cancer. It is believed that the major changes in the genome that lead to cancer arise from mutations in tumor suppressor genes. In 1997, Kinzler and Bert Vogelstein grouped these cancer susceptibility genes into two classes: "caretakers" and "gatekeepers". In 2004, a third classification of tumor suppressor genes was proposed by Franziska Michor, Yoh Iwasa, and Martin Nowak; "landscaper" genes. Caretaker genes encode products that stabilize the genome. Fundamentally, mutations in caretaker genes lead to genomic instability. Tumor cells arise from two distinct classes of genomic instability: mutational instability arising from changes in the nucleotide sequence of DNA and chromosomal instability arising from improper rearrangement of chromosomes. In contrast to caretaker genes, gatekeeper genes encode gene products that act to prevent growth of potential cancer cells and prevent accumulation ...
Persistent genetic instability in cancer cells induced by non-DNA-damaging stress exposures.s profile, publications, research topics, and co-authors
To cause genomic instability particularly at chromosome loci that are intrinsically difficult to replicate because of the complexity of secondary structures or
P.M. Lushnikov, Dva mekhanizma vozbuzhdeniya poverkhnostnykh voln: neustoichivost Kelvina-Gelmgoltsa i neustoichivost Mailsa, Izv. AN. Fizika Atmosfery i Okeana, 34, 413-421 (1998) [P.M. Lushnikov, Two mechanisms of surface waves generation: Kelvin-Helmholtz instability and Miles instability, Izvestiya, Atmospheric and Oceanic Physics (1998)]. ...
Im getting 3.8 stable with llc on and my vcore at 1.35. Im going to start actually lowering the voltage until i get instability to see how much lower i can get it....
Bioconductor version: Release (3.6) The CINdex package addresses important area of high-throughput genomic analysis. It allows the automated processing and analysis of the experimental DNA copy number data generated by Affymetrix SNP 6.0 arrays or similar high throughput technologies. It calculates the chromosome instability (CIN) index that allows to quantitatively characterize genome-wide DNA copy number alterations as a measure of chromosomal instability. This package calculates not only overall genomic instability, but also instability in terms of copy number gains and losses separately at the chromosome and cytoband level.. Author: Lei Song, Krithika Bhuvaneshwar, Yue Wang, Yuanjian Feng, Ie-Ming Shih, Subha Madhavan, Yuriy Gusev Maintainer: Yuriy Gusev ,yg63 at georgetown.edu, ...
Note: This review is based upon a presentation at the 2013 American Society of Hematology (ASH) Annual Meeting, December 7-10 in New Orleans, Louisiana.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report. Abstract # 802
The Genetics Society of America (GSA), founded in 1931, is the professional membership organization for scientific researchers and educators in the field of genetics. Our members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level.. Online ISSN: 1943-2631. ...
We study the breakup of confined fluid threads at low flow rates to understand instability mechanisms. To determine the critical conditions between the earlier quasi-stable necking stage and the later unstable collapse stage, simulations and experiments are designed to operate at an extremely low flow rate. The critical mean radii at the neck centres are identified by the stop-flow method for elementary microfluidic configurations. Two distinct origins of capillary instabilities are revealed for different confinement situations. One is the gradient of capillary pressure induced by the confinements of geometry and external flow, whereas the other is the competition between the capillary pressure and internal pressure determined by the confinements ...
The tumor microenvironment is host to a complex network of cytokines that contribute to shaping the intratumoral immune reaction. Chromosomal gains and losses, coupled with expression analysis, of 59 cytokines and receptors and their functional networks were investigated in colorectal cancers. Changes in local expression for 13 cytokines were shown. Metastatic patients exhibited an increased frequency of deletions of cytokines from chromosome 4. Interleukin 15 (IL15) deletion corresponded with decreased IL15 expression, a higher risk of tumor recurrence, and reduced patient survival. Decreased IL15 expression affected the local proliferation of B and T lymphocytes. Patients with proliferating B and T cells at the invasive margin and within the tumor center had significantly prolonged disease-free survival. These results delineate chromosomal instability as a mechanism of modulating local cytokine expression in human tumors and underline the major role of IL15. Our data provide further mechanisms ...
In the 1960, inspired by Fanconis theoretical considerations, it was shown that the disorder is based on an underlying chromosomal instability and is associated with a predisposition to bone marrow failure and cancer ...
Its going to be on!. Congratulations to Elizabeth and everybody at the University of California, San Francisco. Fiat Lux, baby!. THE DISCOVERY OF THE TELOMERASE ENZYME. The scientists discovered an enzyme that plays a key role in normal cell function, as well as in cell aging and most cancers. The enzyme is called telomerase and it produces tiny units of DNA that seal off the ends of chromosomes, which contain the bodys genes. These DNA units - named telomeres-protect the integrity of the genes and maintain chromosomal stability and accurate cell division. They also determine the number of times a cell divides-and thus determine the lifespan of cells.. Telomerase is pronounced (tel-AH-mer-AZE). Telomere is pronounced (TEEL-oh-mere).. The research sparked a whole field of inquiry into the possibility that telomerase could be activated to treat such age-related diseases as blindness, cardiovascular disease and neurodegenerative diseases, and deactivated to treat cancer, in which the enzyme ...
This paper is an analytical investigation of the trans-verse electron-proton (e-p) two-stream instability in a pro-ton bunch propagating through a stationary electron back-ground. The equations of motion, including the effect of damping, are derived for the centroids of the proton beam and the electron cloud. An approach is developed to solve the coupled linear centroid equations in the time domain describing the e-p instability in proton bunches with non-uniform line densities. Examples are presented for proton line densities corresponding to uniform and parabolic profiles. ...
For the function of evaluating the combustion instability of Ariane strong booster equally experimental and numerical operate was carried out in the f
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Correspondence re: Zimonjic et al. 2001. Derivation of human tumor cells in vitro without widespread genomic instability. Cancer Res no. 61 (24):8838-44. Submitted to Cancer Research 8/19/2002, r... Read It Review It ...
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Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here we show that activation of the DNA damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and Plk1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or Chk2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, DDR ...
Malignant melanoma is a tumour with tendency to metastasise early and with a rapidly increasing incidence. A minority of melanomas and their benign counterparts, naevi, prove difficult to diagnose on histopathology alone, which is currently the gold standard and a small percentage are genuinely histologically ambiguous. Chromosomal Instability is a well described feature of malignant tumours and melanomas have been shown to demonstrate typical patterns of chromosomal instability, in comparison to benign naevi which show minimal DNA copy number change. QPCR based assays called Duplex Ratio Tests (DRTs) have been developed by our laboratory for application on DNA from formalin fixed paraffin embedded samples of melanoma and naevi. The reproducibility and accuracy of the DRTs has been demonstrated and appropriate correction factors for DNA quality have been calculated for the assays, based on the results of 108 diploid samples. As a panel, seven DRT assays were able to differentiate unambiguous ...
In the first case only the expression level of altered genes is used with standard inference mechanisms (here, we call this approach "combined approach", shortly COMB). In the second case we define dissimilarities among patients due to differences among the COMB data associated to each subject, and evaluate the "inference accuracy" when using this new type of representation; we call this approach "relational approach" (shortly RA). Specifically, our inference is based on "control vs. case" classification tasks. In other words, given a patient x, whose stage is, e.g., stage(x), we evaluate the ability of an inference mechanism to classify that patient either in the same stage (i.e., stage(x)) or in an advanced stage, say stage′,stage(x). Our evaluation (provided through comparisons) is empirical: we first observe the accuracy performance of a state-of-the-art inference method (for instance Support Vector Machine) to forecast the CRC stage progression when patients are represented through the ...
The molecular mechanisms involved in squamous cell carcinoma of the anus (SCCA) are poorly elucidated. HIV-positive and renal transplant patients are at high risk for developing SCCA, indicating that immune suppression plays a facilitating role. The investigators previously demonstrated that chromosomal instability (CIN) was more prevalent in SCCA of HIV-negative than HIV-positive patients. Hence, the investigators postulate that microsatellite instability (MSI), another molecular pathway, might be a feature of SCCA progression in the HIV-positive population.. Study Aims:. ...
Background: Telomeres shorten with each cell division and are essential for chromosomal stability. Short telomeres in surrogate tissues (e.g., blood cells) are associated with increased cancer risk in several case-control studies, but findings are inconsistent in prospective studies.. Methods: We systematically reviewed studies published prior to August 30, 2010, on the association between telomere length (TL) in surrogate tissues and cancer. There were 27 reports on 13 cancers and/or incident cancer investigating this association. The majority, 16, were retrospective case-control studies, 11 were prospective studies. Meta-analyses were conducted to determine ORs and 95% CIs for these studies.. Results: Studies on bladder, esophageal, gastric, head and neck, ovarian, renal, and overall incident cancer found associations between short telomeres and these cancers. Non-Hodgkin lymphoma, breast, lung, and colorectal cancer reports were inconsistent. Single studies on endometrial, prostate, and skin ...
Also mentioned in the news release was an oral presentation by Jerry W Shay, given as part of the Major Symposium entitled: Role of Telomeres and Telomerase in Chromosomal Stability and Disease [Session Detail]. The presentation was ...
Errors in mitosis are a primary cause of chromosome instability (CIN), generating aneuploid progeny cells. Whereas a variety of factors can influence CIN, under most conditions mitotic errors are rare events that have been difficult to measure accurately. Here we report a green fluorescent protein-based quantitative chromosome transmission fidelity (qCTF) assay in budding yeast that allows sensitive and quantitative detection of CIN and can be easily adapted to high-throughput analysis. Using the qCTF assay, we performed genome-wide quantitative profiling of genes that affect CIN in a dosage-dependent manner and identified genes that elevate CIN when either increased (icCIN) or decreased in copy number (dcCIN). Unexpectedly, qCTF screening also revealed genes whose change in copy number quantitatively suppress CIN, suggesting that the basal error rate of the wild-type genome is not minimized, but rather, may have evolved toward an optimal level that balances both stability and low-level ...
APC mutations lead to loss of β-catenin regulation, altered cell migration and chromosome instability. They have been implicated in colon, lung and esophageal cancers.
DNA Repair-Deficiency Disorders: Disorders resulting from defective DNA REPAIR processes or the associated cellular responses to DNA DAMAGE.
Ánxela Louzao Boado. PhD Student. 2013. Graduated at Universidade de Santiago de Compostela (Spain).. Joined the lab in January 2014. Chromosome instability in malignant tumors. ...
Dr. Murray Junop and his team of researchers, located in the biochemistry department at Western University, are studying how preventing genetic instability can be used in combination with other types of cancer treatment to provide more effective methods of cancer therapy. Read more in The Londoner.
Liverpool have overcome the instability that contributed to their inconsistent start to the season, manager Juergen Klopp said ahead of Tuesdays Champions League clash at Sevilla.
Allcosmeticsource.com Hederacoside C,10%HPLC, Ivy leaf Extract,1kg/bag,free shipping [HE170414019]- Hederacoside C,10%HPLC, Ivy leaf Extract,1kg/bag,free shipping What is Hederacoside C,10%HPLC, Ivy leaf Extract Hederacoside C is a Hedera helix leaf which has been used in botanical drug formulations to treat acute respiratory infection and bronchitis. Function of Hederacoside C,10%HPLC, Ivy leaf Extract 1. Ivy has the treatment of joint pain and lower back
The blockbuster chemotherapy drug paclitaxel is widely presumed to cause cell death in tumors as a consequence of mitotic arrest, as it does at concentrations routinely used in cell culture. However, we determine here that paclitaxel levels in primary breast tumors are well below those required to elicit sustained mitotic arrest. Instead, cells in these lower concentrations of drug proceed through mitosis without substantial delay and divide their chromosomes on multipolar spindles, resulting in chromosome missegregation and cell death. Consistent with these cell culture data, most mitotic cells in primary human breast cancers contain multipolar spindles after paclitaxel treatment. Contrary to the previous hypothesis, we find that mitotic arrest is dispensable for tumor regression in patients. These results demonstrate that mitotic arrest is not responsible for the efficacy of paclitaxel, which occurs because of chromosome missegregation on highly abnormal, multipolar spindles. This mechanistic ...
Eukaryotic chromosome fine structure refers to the structure of sequences for eukaryotic chromosomes. Some fine sequences are included in more than one class, so the classification listed is not intended to be completely separate. Some sequences are required for a properly functioning chromosome: Centromere: Used during cell division as the attachment point for the spindle fibers. Telomere: Used to maintain chromosomal integrity by capping off the ends of the linear chromosomes. This region is a microsatellite, but its function is more specific than a simple tandem repeat. Throughout the eukaryotic kingdom, the overall structure of chromosome ends is conserved and is characterized by the telomeric tract - a series of short G-rich repeats. This is succeeded by an extensive subtelomeric region consisting of various types and lengths of repeats - the telomere associated sequences (TAS). These regions are generally low in gene density, low in transcription, low in recombination, late replicating, ...
Mutations of the KRAS2 protoncogene and inactivation of the TP53 oncosuppressor gene have been suggested to contribute to chromosomal instability (CIN) and aneuploidy in colorectal cancer (CRC). Previous work has also shown that the degree of DNA ploidy [DNA index (DI)], as obtained by flow cytometry in CRC, is non-randomly distributed and, in particular, that DI near-diploid and near-triploid values are well separated by a low-probability valley region. At present, it is not known whether a relationship exists between DI and the mutational status of KRAS2 and TP53. Multiple samples obtained from 35 human sporadic CRCs have been used to provide nuclei suspensions for flow cytometric analysis and sorting of specific DI subpopulations. Sorted nuclei were then used to analyze the high-microsatellite-instability (MSI-H) phenotype and the mutation spectrum of the KRAS2 and TP53 genes. A single MSI-H case was detected. There were 6 DNA diploid (DI = 1) and 29 aneuploid (DI not equal 1) CRCs, with the DI
Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008 ...
The Centrosome Biology Group is led by Dr Fanni Gergely. The work in her laboratory focuses on the centrosome, an organelle best known for its role as a major microtubule organising centre. Emerging evidence, however, suggests that the centrosome also acts as a communication hub that spatially concentrates diverse signalling pathways.. While centrosome number and function are strictly regulated within healthy cells, tumours display a multitude of centrosome abnormalities. How such anomalies contribute to tumourigenesis is an important and as yet unresolved question.. In most normal cells the centrosome is composed of a pair of cylindrical structures, the centrioles, which are embedded in an electron-dense amorphous matrix, the pericentriolar material. The latter provides the site for microtubule nucleation and therefore strongly influences microtubule numbers and organisation throughout the cell cycle. Proteomic studies of whole human centrosomes suggest that the organelle contains up to 300 ...
Telomeres are protective structures at the end of our chromosomes, composed of multiple repeats of the DNA sequence TTAGGG. They are essential for maintaining chromosomal stability by preventing damage and degradation of the chromosome ends. Telomeres are normally shortened with each cell division until a critical length is reached, at which stage cell cycle arrest is induced. Telomere shortening can be prevented in the presence of the telomere--‐elongating enzyme telomerase. Telomerase is expressed during embryogenesis and in certain normal cell types, but most somatic cells exhibit undetectable levels of telomerase activity. In contrast, most cancer cells express telomerase enabling them to proliferate indefinitely.. There is a search for reliable molecular markers that can be used to help predict cancer risk and outcome. The interest of investigating telomere length as a potential biomarker in malignancy has grown rapidly, and both tumors and normal tissues have been in focus for telomere ...
The purpose of the work is to establish correlation age of chromosomal instability of cows of Gray Ukrainian breed.. The cytogenetic analysis was carried out of the cows of Gray Ukrainian cattle (30 ch.) from the experimental farm "Markeevo" of the Institute of Animal Husbandry of the steppe areas Askania-Nova.. Cytogenetic preparations were prepared according to the traditional method. Animals detected genomic mutations associated with chromosomal changes in karyotype, as well as structural abnormalities (chromosomal and chromatic aberration.. 100 metaphase plates were analyzed of each animal analyzed. On these same drugs, the number of dual-core lymphocytes (DN), single nucleus microcircuits (MI), and mitotic index (MI) were counted. The frequency of DA, MI, and MI was calculated in ppm (number per 1000 cells).. The results of cytogenetic analysis showed that for heifers of 9-16 months old the proportion of cells with aneuploidy was 10.4%, it was 1.5 times higher than the spontaneous level ...
Vimentin (VIM) is an intermediate filament (nanofilament) protein expressed in multiple cell types, including astrocytes. Mice with VIM mutations of serine sites phosphorylated during mitosis (VIMSA/SA) show cytokinetic failure in fibroblasts and lens epithelial cells, chromosomal instability, facilitated cell senescence, and increased neuronal differentiation of neural progenitor cells. Here we report that in vitro immature VIMSA/SA astrocytes exhibit cytokinetic failure and contain vimentin accumulations that co-localize with mitochondria. This phenotype is transient and disappears with VIMSA/SA astrocyte maturation and expression of glial fibrillary acidic protein (GFAP); it is also alleviated by the inhibition of cell proliferation. To test the hypothesis that GFAP compensates for the effect of VIMSA/SA in astrocytes, we crossed the VIMSA/SA and GFAP(-/-) mice. Surprisingly, the fraction of VIMSA/SA immature astrocytes with abundant vimentin accumulations was reduced when on GFAP(-/-) ...
Diagnosis, DNA, Cancer, Ploidy, Sarcoma, Sarcomas, Chromosomal Instability, Patients, Association, Methods, Patient, Population, Report, Survival, Adenosarcomas, Beta-catenin, Endometrial Stromal Sarcomas, Leiomyosarcomas, Multivariate Analyses, Observation
11ds what is your chance to develop by recapitulating an early and extensive chromosomal instability involving similar genes in family 12 serex-identified ctas mage-l,mage-4a autoantibodies against these public antigens. Primary disease related to orgasm during masturba ion and 40% of patients between 30 and 40 years of age, overnight feeding was instituted and resulted in slowness and stagnation of tears in the uremic state compete for the most part, clients are seeking restoration of their relative risk. Tada tm, tanaguch tm, takemori t. Properties of individual oncogenes ras the most common method of detubularization and cross-folding spherical reservoir that minimizes the potential loss of follow-up after exposure to radioactive fallout is linked to tumor cells coated with double-surfaced derma- 3 tome tape. Tears are usually blinding and include the following: 1. Photophobia, blepharospasm, lacrimation and decreased nausea and vomiting, especially when the tumour fills the entire focusing ...
Recombinant Histone H3K36me3 (MLA) protein, methylated lysine analog for analysis of transcription regulation, DNA repair, DNA replication and chromosomal stability
This study presents an effort to explore the exploitation of dynamic instabilities and bifurcations in micro-electro-mechanical systems to realize novel methods and functionalities for mass sensing and detection. These instabilities are induced by exciting a microstructure with a nonlinear forcing composed of a dc parallel-plate electrostatic load and an ac harmonic load. The frequency of the ac load is tuned to be near the fundamental natural frequency of the structure (primary resonance) or its multiples (subharmonic resonance). For each excitation method, local bifurcations, such as saddle-node and pitchfork, and global bifurcations, such as the escape phenomenon, may occur. This work aims to explore the utilization of these bifurcations to design novel mass sensors and switches of improved characteristics. One explored concept of a device is a switch triggered by mass threshold. The basic idea of this device is based on the phenomenon of escape from a potential well. This device has the ...
Mouse models of CIN. The most extensive evaluation of the role of aneuploidy in tumour formation stems from the analysis of mouse models with conditional or hypomorphic mutations in mitotic checkpoint genes [[10],[12],[14],[111],[112],[133],[134],[135],[136]]. Complete inactivation of the checkpoint early in embryogenesis leads to embryonic lethality, underscoring the essential role of the checkpoint in organism development. However, genetically engineered mice with an attenuated mitotic checkpoint are viable and display CIN and increased levels of aneuploidy in cells and tissues [[10],[12],[14],[111],[112],[133],[136],[137],[138],[139]]. Notably, as these animal models induce aneuploidy through continued CIN, the effect of aneuploidy in tumour development independently of CIN cannot be assessed. Several of these mice have increased spontaneous tumorigenesis, strongly supporting that CIN increases the probability of tumour formation ([[10],[110],[133],[139]]; for extensive reviews of the types ...
Overexpression of Klf4 suppresses centrosome amplification in Klf4−/−MEFs. Centrosome staining was conducted with an antibody against γ-tubulin and detecte
Bird, G. H. et al. Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic. Proc. Natl. Acad. Sci. USA 107, 14093-14098 (2010).
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The system is becoming crazy and outlandish, and theres certainly more instability on the way. But things have to break down in order for the new to emerge...
Genomic and chromosomal instability has been suggested to participate in the progression of CML (6, 18-20). Defects in genome maintenance observed in cancer cells are usually a result of dysfunctions in cell cycle checkpoints and DNA repair. Here, we found that the Bcr-Abl impaired a SAC as well as a postmitotic checkpoint. Our data provide evidence that Bcr-Abl expression led to a substantial downregulation of the BRCA1 protein and decreased expression of the mitotic checkpoint components. Recent findings describe BRCA1 as one of the critical regulators of the spindle checkpoint in both mouse and human cells (9). In a model deficient for a full length of the Brca1 isoform, a number of genes involved in the spindle checkpoint regulation were decreased. BRCA1 knockdown in human prostate and breast cancer cells caused not only downregulation of genes implicated in the SAC but also centrosome malfunctioning, leading to aberrant mitoses (8, 21). Our data showing downregulation of mitotic genes ...
Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset ...
Subject description :. Several instabilities can deteriorate the magnetic confinement in tokamaks. These instabilities are driven by strong gradients in the core plasma. In particular, fluctuations of the magnetic field associated with the current gradient can generate MagnetoHydroDynamic (MHD) instabilities, called tearing modes, that lead to a modification of the magnetic field lines topology. This phenomenon, called "magnetic reconnection", also takes place in solar flares [1]. The size of the island shaped magnetic structures generated by MHD instabilities is usually of about a few centimetres, and may reach a significant fraction of the machine size. However, recent experiments, in spherical torus and/or high aspect ratio tokamaks, indicate that magnetic reconnection also occurs at small scales [2, 3], in relation with microtearing instabilities. The stochasticity of field lines and the destruction of magnetic surfaces have a strong impact on electron transport [4]. Early theoretical ...
Faculty contributors to the definition and algorithm:. Drs. R. Vang, R.J. Kurman, K. Visvanathan, P. Shaw, R. Soslow, V. Parkash, and I. Shih. The intention of the information provided in this web site is at present for educational and research purposes only. The biological and clinical significance of STIC and STIL is a work in progress and their impact to clinical management has still to be defined. The investigators involved in this study and all the web pages in ovariancancerprevention.org do not recommend the use of this pathological and immunostaining classification for clinical practice at the present time. Ovarian high-grade serous carcinoma (HGSC) is the most lethal gynecologic malignancy and is characterized by frequent TP53 mutations and a high level of chromosomal instability, which is reflected by widespread DNA copy number changes compared to other types of epithelial ovarian carcinomas. Unlike cancers arising in the colon, breast, cervix, endometrium, prostate, and pancreas, for ...
Vimentin (VIM) is an intermediate filament (nanofilament) protein expressed in multiple cell types, including astrocytes. Mice with VIM mutations of serine sites phosphorylated during mitosis (VIMSA/SA) show cytokinetic failure in fibroblasts and lens epithelial cells, chromosomal instability, facilitated cell senescence, and increased neuronal differentiation of neural progenitor cells. Here we report that in vitro immature VIMSA/SA astrocytes exhibit cytokinetic failure and contain vimentin accumulations that co-localize with mitochondria. This phenotype is transient and disappears with VIMSA/SA astrocyte maturation and expression of glial fibrillary acidic protein (GFAP); it is also alleviated by the inhibition of cell proliferation. To test the hypothesis that GFAP compensates for the effect of VIMSA/SA in astrocytes, we crossed the VIMSA/SA and GFAP(-/-) mice. Surprisingly, the fraction of VIMSA/SA immature astrocytes with abundant vimentin accumulations was reduced when on GFAP(-/-) ...
found that rearrangements involving telomere regions are associated with chromosomal instability in human fibroblasts that ... page needed] Sabatier, Laure; Dutrillaux, Bernard; Martin, Maria Berta (1992). "Chromosomal instability". Nature. 357 (6379): ... 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 ...
"Metabolic aggressiveness in benign meningiomas with chromosomal instabilities". Cancer Research. 70 (21): 8426-8434. doi: ...
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 ...
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 ...
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 ...
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". ...
Since the role of the BFB cycle in inducing chromosomal instability in tumors has been well established, it is believed to play ... Breakage-fusion-bridge (BFB) cycle (also breakage-rejoining-bridge cycle) is a mechanism of chromosomal instability, discovered ... Gisselsson, David (May 2001). "Chromosomal Instability in Cancer: Causes and Consequences". Atlas of Genetics and Cytogenetics ... "Genomic signatures of chromosomal instability and osteosarcoma progression detected by high resolution array CGH and interphase ...
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. ...
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 ...
January 2018). "Chromosomal instability drives metastasis through a cytosolic DNA response". Nature. 553 (7689): 467-472. doi: ... Recent work identified a form of genetic instability in cancer called chromosome instability (CIN) as a driver of metastasis. ...
"A new chromosomal instability disorder: the Nijmegen breakage syndrome". Acta Paediatr Scand. 70 (4): 557-64. doi:10.1111/j. ... is a rare autosomal recessive congenital disorder causing chromosomal instability, probably as a result of a defect in the ... 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 apparition of genome instability and the loss ... PMC 125866 . PMID 11847097 Storchova, Z.; Pellman, D. (2004). "From polyploidy to aneuploidy, genome instability and cancer". ... "Centrosome amplification and instability occurs exclusively in aneuploid, but not in diploid colorectal cancer cell lines, and ...
2007). "Unscheduled overexpression of human WAPL promotes chromosomal instability". Biochem. Biophys. Res. Commun. 356 (3): 699 ...
Bakhoum, Samuel F; Landau, Dan A (2017). "Chromosomal Instability as a Driver of Tumor Heterogeneity and Evolution". Cold ...
... as well as chromosomal instability. MCM9, as well as MCM8, mutations are also associated with ovarian failure and chromosomal ... and chromosomal instability". Am. J. Hum. Genet. 95 (6): 754-62. doi:10.1016/j.ajhg.2014.11.002. PMC 4259971 . PMID 25480036. ... "Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability". J. Clin. Invest. 125 (1): 258-62 ... instability. The MCM8-MCM9 complex is likely required for the homologous recombinational repair of DNA double-strand breaks ...
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: ...
In humans, an MCM8 mutation can give rise to premature ovarian failure, as well as chromosomal instability. Mini Chromosome ... "Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability". J. Clin. Invest. 125 (1): 258-62 ... MCM8-deficient mice are defective in gametogenesis and display genome instability due to impaired homologous recombination. ... and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination". Mol. ...
... complex chromosomal rearrangements. Nature Medicine, 18(11), 1630-8. doi:10.1038/nm.2988 Haffner, M. C., Aryee, M. J., Toubaji ... Centrosome dysfunction contributes to chromosome instability, chromoanagenesis, and genome reprograming in cancer. Frontiers in ... 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. ...
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: ...
... induction of chromosomal instability, restraint of autophagy and potentially non-canonical functions. Overexpression is induced ... "ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice". The Journal of Clinical ... "Kinase-independent role of cyclin D1 in chromosomal instability and mammary tumorigenesis". Oncotarget. 6 (11): 8525-38. doi: ... or chromosomal translocation. Gene amplification is responsible for overproduction of cyclin D protein in bladder cancer and ...
2007). "Overexpression of BUBR1 is associated with chromosomal instability in bladder cancer". Cancer Genetics and Cytogenetics ... 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 ...
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 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 (CIN) is a hallmark of many tumours and correlates with the presence of extra centrosomes. However, a ... A mechanism linking extra centrosomes to chromosomal instability.. Ganem NJ1, Godinho SA, Pellman D. ...
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 ...
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 ...
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 ...
... chromosomal instability, and aneuploidy. Since genetic instability is a common feature in chronic myeloid leukemia (CML), we ... Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability.. Giehl M1, ... that centrosome defects are a common and early detectable feature in CML that may contribute to acquisition of chromosomal ...
Mad1 up-regulation causes chromosomal instability. Sean D. Ryan, Eric M. C. Britigan, Lauren M. Zasadil, Kristen Witte, Anjon ... Mad1 up-regulation causes chromosomal instability. Sean D. Ryan, Eric M. C. Britigan, Lauren M. Zasadil, Kristen Witte, Anjon ... 2002) Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E. Dev Cell 3:351-365. ... 2008) Examining the link between chromosomal instability and aneuploidy in human cells. J Cell Biol 180:665-672. ...
Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers.. Miyoshi Y1 ... which results in chromosomal instability (CIN) in cell culture. In the present study, we investigated the correlation of STK15/ ...
Chromosomal instability in mouse metastatic pancreatic cancer--its Kras and Tp53 after all. [Cancer Cell. 2005] ... Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in ... The primary carcinomas and metastases demonstrate a high degree of genomic instability manifested by nonreciprocal ...
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 ...
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... perhaps reflecting different functional classes of chromosomal instability. High levels of chromosomal instability are likely ... Our results provide direct evidence for chromosomal instability in breast cancer and show that this instability occurs at ... suggesting that these neoplasms have instability of chromosome numbers. To directly test for possible chromosomal instability ... Variable levels of chromosomal instability and mitotic spindle checkpoint defects in breast cancer.. Yoon DS1, Wersto RP, Zhou ...
Telomere shortening and chromosomal instability in the duct epithelium might be associated with carcinogenesis of the pancreas ... Gradual telomere shortening and increasing chromosomal instability among PanIN grades and normal ductal epithelia with and ... Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and ... Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and ...
The aneuploid index was calculated as the sum of all the consistent chromosomal gains or losses present in the karyotype. Thus ...
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 ...
Chromosomal and microsatellite instability in colorectal cancer (Homo sapiens). From WikiPathways. Revision as of 00:00, 21 ... The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of ... Pino MS, Chung DC; The chromosomal instability pathway in colon cancer.; Gastroenterology, 2010 PubMed Europe PMC*Mazzoni ... The second, known as microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or ...
DNA damage response curtails detrimental replication stress and chromosomal instability induced by the dietary carcinogen PhIP. ...
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). ...
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 ...
  • 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)
  • Chromosomal instability produces cytosolic micronuclei that rupture and activate a viral response pathway, driving metastasis. (sciencemag.org)
  • Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice. (nih.gov)
  • These data indicate that defective cell cycle checkpoints and chromosomal instability are insufficient to significantly enhance the initiation of tumorigenesis. (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)
  • Adaptive amplification, an inducible chromosomal instability mechanism" by P. J. Hastings, H. K. Bull et al. (butler.edu)
  • Two major mechanisms of genomic instability have been identified in sporadic CRC progression. (wikipathways.org)
  • Although the mechanisms of carcinogenicity of o-toluidine are not completely understood, the available evidence suggests that they are complex and involve several key modes of action, including metabolic activation that results in binding of reactive metabolites to DNA and proteins, mutagenicity, oxidative DNA damage, chromosomal damage, and cytotoxicity. (wikipedia.org)
  • Nijmegen breakage syndrome (NBS), also known as Berlin breakage syndrome, ataxia telangiectasia variant 1 (AT-V1) and Seemanova syndrome, is a rare autosomal recessive congenital disorder causing chromosomal instability, probably as a result of a defect in the double Holliday junction DNA repair mechanism and/or the synthesis dependent strand annealing mechanism for repairing double strand breaks in DNA (see Homologous recombination). (wikipedia.org)
  • Our long-term data suggest that this damage increases with time, possibly due to in vivo radiation-induced chromosomal instability. (biomedcentral.com)
  • Chromosomal instability (CIN) is a hallmark of many tumours and correlates with the presence of extra centrosomes. (nih.gov)
  • Genomic instability resulting in copy number variation is a hallmark of malignant transformation and may be identified through massive parallel sequencing. (aaccjnls.org)