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.Cell Line, Tumor: A cell line derived from cultured tumor cells.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).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.Tumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.Karyotyping: Mapping of the KARYOTYPE of a cell.Chromosome Fragility: Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.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.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.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.Chromosome Breakage: A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.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.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).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.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.Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.Tumor Burden: The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.Ploidies: The degree of replication of the chromosome set in the karyotype.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.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.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)DNA, Neoplasm: DNA present in neoplastic tissue.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.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.Polyploidy: The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.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.Genes, Tumor Suppressor: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.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.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.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.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)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.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.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.Wilms Tumor: A malignant kidney tumor, caused by the uncontrolled multiplication of renal stem (blastemal), stromal (STROMAL CELLS), and epithelial (EPITHELIAL CELLS) elements. However, not all three are present in every case. Several genes or chromosomal areas have been associated with Wilms tumor which is usually found in childhood as a firm lump in a child's side or ABDOMEN.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.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.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.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.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.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.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.Telomerase: An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.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.)Colonic Neoplasms: Tumors or cancer of the COLON.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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).Carcinoid Tumor: A usually small, slow-growing neoplasm composed of islands of rounded, oxyphilic, or spindle-shaped cells of medium size, with moderately small vesicular nuclei, and covered by intact mucosa with a yellow cut surface. The tumor can occur anywhere in the gastrointestinal tract (and in the lungs and other sites); approximately 90% arise in the appendix. It is now established that these tumors are of neuroendocrine origin and derive from a primitive stem cell. (From Stedman, 25th ed & Holland et al., Cancer Medicine, 3d ed, p1182)Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.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.Diploidy: The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.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.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)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.Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.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.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.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.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.Neuroendocrine Tumors: Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via APUD CELLS), the presence of tumor-associated antigens, and isozyme composition.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.Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.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.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.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.Tumor Microenvironment: The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Breast Neoplasms: Tumors or cancer of the human BREAST.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.Neoplasm Staging: Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.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.Mammary Neoplasms, Experimental: Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.DNA Breaks, Double-Stranded: Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.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.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.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.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.Mice, Inbred C57BLCarcinoma, Squamous Cell: A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)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.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.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Adenoma: A benign epithelial tumor with a glandular organization.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.Liver Neoplasms: Tumors or cancer of the LIVER.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.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.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.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)Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.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.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.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Meningioma: A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7)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.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Chromosomes, Human, Pair 4: A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.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).Chromosomes, Human, Pair 17: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.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.Anaphase: The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.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.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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.DNA Replication: The process by which a DNA molecule is duplicated.Transplantation, Heterologous: Transplantation between animals of different species.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.Precancerous Conditions: Pathological processes that tend eventually to become malignant. (From Dorland, 27th 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.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.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.Allelic Imbalance: A situation where one member (allele) of a gene pair is lost (LOSS OF HETEROZYGOSITY) or amplified.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.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.Cytokinesis: The process by which the CYTOPLASM of a cell is divided.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.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.Gastrointestinal Stromal Tumors: All tumors in the GASTROINTESTINAL TRACT arising from mesenchymal cells (MESODERM) except those of smooth muscle cells (LEIOMYOMA) or Schwann cells (SCHWANNOMA).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.Chromosome Deletion: Actual loss of portion of a chromosome.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Chromosomes, Human, Pair 7: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.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.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 18.104.22.168.Mice, Inbred BALB CCpG 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.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.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.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 enzymesRad51 Recombinase: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.Mitotic Index: An expression of the number of mitoses found in a stated number of cells.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.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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Carcinogens: Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.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.Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.Cell Growth Processes: Processes required for CELL ENLARGEMENT and CELL PROLIFERATION.Nocodazole: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.Tetraploidy: The presence of four sets of chromosomes. It is associated with ABNORMALITIES, MULTIPLE; and MISCARRAGES.Gonadal Disorders: Pathological processes of the OVARIES or the TESTES.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.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)Chromosomes, Human, Pair 20: A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.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.Carcinoma, Hepatocellular: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Fibrosarcoma: A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)Antigens, Nuclear: Immunologically detectable substances found in the CELL NUCLEUS.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.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.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Skin Neoplasms: Tumors or cancer of the SKIN.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.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.Kidney Neoplasms: Tumors or cancers of the KIDNEY.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.Genes, Neoplasm: Genes whose abnormal expression, or MUTATION are associated with the development, growth, or progression of NEOPLASMS.Adenomatous Polyposis Coli Protein: A negative regulator of beta-catenin signaling which is mutant in ADENOMATOUS POLYPOSIS COLI and GARDNER SYNDROME.Oncogenes: Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.HCT116 Cells: Human COLORECTAL CARCINOMA cell line.Carcinoma, Ehrlich Tumor: A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.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.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.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)Glioma: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)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 Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
"Centrosome amplification drives chromosomal instability in breast tumor development". Proc Natl Acad Sci USA. 99 (4): 1978-1983 ... Nevertheless, it is clear that the presence of an excess of centrosomes is a common event in human tumors. It has been observed ... The presence of an inadequate number of centrosomes is very often linked to the apparition of genome instability and the loss ... This initial observation was subsequently extended to many types of human tumors. Centrosome alterations in cancer can be ...
Bakhoum, Samuel F; Landau, Dan A (2017). "Chromosomal Instability as a Driver of Tumor Heterogeneity and Evolution". Cold ... In February 2016, the Center started a collaboration with IBM to create a tumor registry matching tumor characteristics and ... Two years prior to this, the Center and IBM collaborated on development of an early version of the tumor registry focused on ... Cha, Ariana Eunjung (25 February 2016). "IBM and New York Genome Center's new cancer tumor repository aims to revolutionize ...
Chromosomal rearrangement due to genome instability can cause gene amplification and deletion. Gene amplification is the ... which occur frequently in solid tumors, and can contribute to tumor evolution through altered gene expression. Hamster cell ... In the rat, an NF-κB binding site is adjacent to the mdr1b gene, NF-κB can be active in tumour cells because its mutated NF-κB ... Tumors with loss of ER and PR no longer respond to tamoxifen or other anti-estrogen treatments, and while cancer cells remain ...
SIRT2 has been proposed to act as a tumor suppressor by preventing chromosomal instability during mitosis. SIRT2-specific ... SIRT2 may suppress or promote tumor growth in a context-dependent manner. ... "The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 ... thereby regulating chromosomal condensation during mitosis. During the cell cycle, SIRT2 associates with several mitotic ...
Aoki K, Tamai Y, Horiike S, Oshima M, Taketo MM (2003). "Colonic polyposis caused by mTOR-mediated chromosomal instability in ... The Min mouse can develop up to 100 polyps in the small intestine in addition to colon tumors. Later, new knock-out mutants of ... Poole AJ, Heap D, Carroll RE, Tyner AL (2004). "Tumor suppressor functions for the Cdk inhibitor p21 in the mouse colon". ... Maltzman T, Whittington J, Driggers L, Stephens J, Ahnen D (1997). "AOM-induced mouse colon tumors do not express full-length ...
In the last stage, progression, the tumor has become karyotypically instable: morphological changes in the normal chromosomal ... This instability is caused by additional mutations. This leads to metastasis, hyperproliferation and loss of control by the ... Second stage tumor promoters like mezerein do not have the capacity to initiate tumors, but can create circumstances in which ... This might also correlate with mezerein being a weak tumor promotor. Robertson, John. "The Poison Garden". The Poison Garden ...
The genetic mutations seen in serous carcinoma are chromosomal instability and mutations in TP53, an important tumor suppressor ... Tumors with high progesterone receptor expression have a good prognosis compared to tumors with low progesterone receptor ... They have a worse prognosis than grade III tumors. Histologically, these tumors show sheets of identical epithelial cells with ... Specifically, ovarian granulosa cell tumors and thecomas are tumors associated with endometrial cancer. Low immune function has ...
Loss-of-function mutations or absence of Bub1 has been reported to result in aneuploidy, chromosomal instability (CIN) and ... of all solid tumors. Loss-of-function mutations or reduced gene expression of Bub1 have been identified in several human tumors ... More precisely, mutations in the spindle checkpoint can lead to chromosomal instability and aneuploidy, a feature present in ... Similarly to its role in kinetochore assembly, it recruits members of the chromosomal passenger complex (CPC) like Aurora B ...
... also known as genome instability. Genomic integrity is now appreciated at several levels where some tumors display instability ... 2007). "Overexpression of BUBR1 is associated with chromosomal instability in bladder cancer". Cancer Genetics and Cytogenetics ... Key tumor suppressors such as p53 also play a role in the spindle checkpoint. Absence of p53, the most commonly mutated gene in ... Most solid tumors are also predominantly aneuploid. For colorectal cancer, BUB1 and BUBR1 and amplification of STK15 are key ...
... can lead to genome instability, cancer, and ageing. The events that lead to genome instability occur in the ... The two processes that are responsible for damage to the S phase are oncogenic activation and tumor suppressor inactivation. ... Disturbance to this phase can generate negative effects, such as inaccurate chromosomal segregation, for the upcoming mitotic ... Normal replicative stress occurs at low to mild levels and induces genomic instability, which can lead to tumorigenesis and ...
DCC would fall into the chromosomal instability category. The chromosomal region of 18q has shown consistent LOH for nearly ... This increase in DCC loss in advanced cancer may indicate that DCC loss is more important to tumour progression than tumour ... 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 ...
This instability, defined as frequent changes in chromosomal structure and number, may be the basis of the development of ... While the frequency of chromatin bridges may be greater in tumor cells relative to normal cells, it may not be practical to ... and chromosomal instability in head and neck tumours with dysfunctional telomeres". British Journal of Cancer. 87 (2): 202-7. ... As a result, several forms of chromosomal aberrations occur, including, but not limited to, binucleated cells, multipolar ...
Chromosomal instability (CIN) which have allelic imbalance at a number of chromosomal loci, including 5q, 8p, 17p, and 18q (Fig ... In these tumors, the INI1 gene (SMARCB1)on chromosome 22q functions as a classic tumor suppressor gene. Inactivation of INI1 ... Deletions in tumor cells may represent the inactivation of a tumor suppressor gene, and may have diagnostic, prognostic, or ... Because SNP array karyotyping can be performed on paraffin embedded tumors, it is an attractive option when tumor cells fail to ...
... chromosomal instability, Barrett's oesophagus and oesohago-gastric carcinoma, cell fate and cancer, lung tumour evolution, ... cancer metabolism, lymphatics and the tumour microenvironment, and cancer metastasis. MRC CU website About Us section MRC CU ...
Since the role of the BFB cycle in inducing chromosomal instability in tumors has been well established, it is believed to play ... The presence of chromosomal aberrations has been demonstrated in every type of malignant tumor. ... 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 ...
... are usually seen before the tumor cells become immortalized and aneuploid which can contribute to the chromosomal instability ... High levels of nuclear cyclin B1 is associated with high tumor grade, larger tumor size and higher metastasis probability, ... "Immune recognition of cyclin B1 as a tumor antigen is a result of its overexpression in human tumors that is caused by non- ... previous work has shown that down regulation of cyclin B1 can lead to tumor regression. A possible treatment option for tumor ...
... whilst chromosomal instability and in vivo suppression are concurrent with a prolonged expression. Multiple miR-744 binding ... miR-744 plays a role in tumour development and growth in mouse cell lines. Its expression induces cyclin B1 expression, whilst ...
Hypomethylation, in general, arises earlier and is linked to chromosomal instability and loss of imprinting, whereas ... Since many tumor suppressor genes are silenced by DNA methylation during carcinogenesis, there have been attempts to re-express ... Furthermore, this study showed that there is a similarity between B cell tumors and long-lived B cells in their DNA methylation ... However, it is currently unclear whether targeting DNMT1 alone is sufficient to reactivate tumor suppressor genes silenced by ...
Tumor cells arise from two distinct classes of genomic instability: mutational instability arising from changes in the ... Chromosomal instability resulting from dysfunctional caretaker genes is the most common form of genetic instability that leads ... Michor, F; Iwasa, Y; Komarova, N. L.; Nowak, M. A. (2003). "Local regulation of homeostasis favors chromosomal instability". ... a tumor suppressor that is consistently found to be mutated in colorectal tumors. Gatekeeper genes are in fact specific to the ...
... induction of chromosomal instability, restraint of autophagy and potentially non-canonical functions. Overexpression is induced ... Additionally, the development of cancer is also enhanced by the fact that retinoblastoma tumor suppressor protein (Rb), one of ... "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: ...
... chromosomal instability is known to be induced by aromatic amines in urinary bladder cells. Chromosomal instability may lead to ... The statistically significant increase of incidences of malignant tumors or benign and malignant tumors combined at several ... loss of the entire gene and the surrounding chromosomal region), which can result in the absence of a tumor suppressor gene ( ... The observation of tumors at tissue sites in addition to the urinary bladder supported the conclusion that o-toluidine was a ...
It can directly target the histone H2AX 3'UTR, reduce histone H2AX expression and induce chromosomal instability after DNA ... Cyclin D1 (CCND1), which is widely upregulated in NPC tumors, is found as a direct target of miR-138. Therefore, miR-138 might ... Therefore, miR-138, by virtue of a BCR-ABL/GATA1/miR-138 circuitry, is a tumor suppressor miRNA implicated in the pathogenesis ... Rhoc, ROCK2 and Tongue cancer Tumour metastasis concerning the Tongue Squamous Cell Carcinoma (TSCC) can be regulated via the ...
"The role of chromosomal instability in tumor initiation", Proc. Natl. Acad. Sci. USA, 99 (25): 16226-31, doi:10.1073/pnas. ... Genome instability can refer to the accumulation of extra copies of DNA or chromosomes, chromosomal translocations, chromosomal ... Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome ... also genetic instability, or even chromosomic instability). The process of genome instability often leads to a situation of ...
benign tumors. A majority of human solid malignant tumors is characterized by chromosomal instability, and have gain or loss of ... which may result in chromosomal instability. Chromosomal instability can in turn cause cancer. However, chromosomal instability ... The research associated with chromosomal instability is associated with solid tumors, which are tumors that refer to a solid ... the majority of colorectal and other solid cancers have chromosomal instability (CIN). This shows that chromosomal instability ...
Low SMUG1 expression is also associated with BRCA1, ATM, XRCC1, implying genomic instability in SMUG1 low tumors. Preclinical ... Low SMUG1 transcripts can impair DNA repair and thus increase mutation rate, enhance chromosomal instability and promote ... SI: DNA Repair and Genetic Instability. 743-744: 26-32. doi:10.1016/j.mrfmmm.2012.12.001. PMC 3616158 . PMID 23253900. Rual JF ... potentially used as a predictive biomarkers of drug response and a mechanism for acquired resistance in certain types of tumors ...
"Chromosomal instability in gastric mucosa-associated lymphoid tissue lymphomas: A fluorescent in situ hybridization study using ... Cells, circulating tumor cells (CTCs), or formalin-fixed paraffin-embedded (FFPE) or frozen tissue sections are fixed, then ... Currently, this type of analysis will only detect gains and losses of chromosomal material and will not detect balanced ... FISH is used by examining the cellular reproduction cycle, specifically interphase of the nuclei for any chromosomal ...
Mutations in the APC tumour suppressor gene cause chromosomal instability. R Fodde. Department of Human and Clinical Genetics, ... We propose that early and transient telomere dysfunction is a major mechanism underlying chromosomal instability of human ... The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF. Fumihiko Hamada. MRC ... Tumor-associated NH2-terminal fragments are the most stable part of the adenomatous polyposis coli protein and can be regulated ...
However, its contribution to tumor development is unclear. Using a new inducible knock-in mouse model we report here that Plk1 ... is overexpressed in a wide spectrum of human tumors, being frequently considered as an oncogene and an attractive cancer target ... Plk1 overexpression induces chromosomal instability and suppresses tumor development Nat Commun. 2018 Aug 1;9(1):3012. doi: ... However, its contribution to tumor development is unclear. Using a new inducible knock-in mouse model we report here that Plk1 ...
Chromosomal Instability Affects the Tumorigenicity of Glioblastoma Tumor-Initiating Cells. Kristina M. Godek, Monica Venere, ... Chromosomal Instability Affects the Tumorigenicity of Glioblastoma Tumor-Initiating Cells. Kristina M. Godek, Monica Venere, ... Chromosomal Instability Affects the Tumorigenicity of Glioblastoma Tumor-Initiating Cells. Kristina M. Godek, Monica Venere, ... Chromosomal Instability Affects the Tumorigenicity of Glioblastoma Tumor-Initiating Cells Message Subject (Your Name) has ...
No Increase in Numerical Chromosomal Instability Compared to Sporadic Tumors ... Chromosomal instability (CIN) as part of genomic instability is an inherent characteristic of most solid tumors and is also ... No Increase in Numerical Chromosomal Instability Compared to Sporadic Tumors. 2011-10-24T00:00:00Z (GMT) by Focken T. ... In this study, we determined the extent of CIN in 32 breast cancer tumors of women with a ,i,BRCA1 ,/i,germline mutation ...
... chromosomal instability, and hepatitis C virus-associated liver cancer.: Hepatitis C virus (HCV) is the only known RNA virus ... Tumor suppressors, chromosomal instability, and hepatitis C virus-associated liver cancer.. Authors * McGivern, David R1 ... Dysfunctional DNA damage and mitotic spindle checkpoints resulting from these interactions may promote chromosomal instability ... but chronic immune-mediated inflammation and associated oxidative chromosomal DNA damage probably play a role. Compelling data ...
Centrosome amplification drives chromosomal instability in breast tumor development. Wilma L. Lingle, Susan L. Barrett, Vivian ... Fingerprint Dive into the research topics of Centrosome amplification drives chromosomal instability in breast tumor ...
DAndrea Lab: Understanding Chromosomal Instability Syndromes Alan DAndrea, MD, is studying the molecular signaling pathways ... Makrigiorgos Lab: Identifying Tumor Signatures Gerassimos (Mike) Makrigiorgos, PhD, is studying the identification and tracing ... DAndreas focus is the molecular pathogenesis of the human chromosomal instability syndromes: Fanconi anemia (FA), ataxia- ... Mouw Lab: DNA Repair Pathway Alterations in Tumors Kent Mouw, MD, PhD, is using a combination of genomic and functional ...
Tumor-Infiltrating Lymphocytes (TILs) and Chromosomal Instability in Patients With CRC. *The Role of TH9/IL-9, TH17/IL-17, and ... Tumor-Infiltrating Lymphocytes (TILs) and Chromosomal Instability in Patients With CRC. TILs in colorectal adenoma/CRC have ... IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived ... Tumor infiltrating T lymphocytes in colorectal cancer: tumor-selective activation and cytotoxic activity in situ. Ann Surg. ( ...
Cancer chromosomal instability: therapeutic and diagnostic challenges: Exploring aneuploidy: the significance of chromosomal ... The corresponding phenotype is termed chromosomal instability (CIN) phenotype. It has been reported that as much as 87% of all ... Chromosomal Instability Substantiates Poor Prognosis in Patients with Diffuse Large B-cell Lymphoma ... Many cancers are characterized by chromosomal instability (CIN). This phenotype involves the deletion and duplication of ...
Chemotherapeutic Effects on Mammalian Tumor Cells. II. Biologic and Chromosomal Instability of a Cyclophosphamide Treated ... Murine leukemia L1210 has been treated with cyclophosphamide and 4 sublines have been developed from the tumor cells surviving ... Biologic studies have demonstrated a marked alteration of virulence compared to the parent tumor and striking cytogenetic ... examinations over an interval of 22 weekly transplant generations have demonstrated a biologic and cytogenetic instability ...
Translocation/chromosomal aberration/genomic instability. Neoplastic cells typically possess various genomic mutations and ... The tumor cell lines also differ in terms of their tumorigenicity. For example, the ff-2 tumor does not take in adults of any ... Xenopus ovarian tumors. Ovarian tumors are poorly described in amphibians (11). Over the 15 years that we have established our ... Slides of these tumors were submitted to the Registry of Tumors in Lower Animals in May of 2000. Hematoxylin and eosin staining ...
... indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability ...
Chlorinated water influences the development of colorectal tumors with chromosomal instability.Dec 31, 2014. ...
Here, the authors highlight the intra-tumour heterogeneity of this disease, finding that spatially closer tumour sectors are ... finding that spatially closer tumour sectors are genetically more similar and that intra-hepatic metastasis is accompanied by ... Here, the authors highlight the intra-tumour heterogeneity of this disease, ... The role of chromosomal instability in tumor initiation. . Proc. Natl Acad. Sci. USA 99, 16226-16231 (2002). ...
Biomarkers, Tumor / genetics* * Biomarkers, Tumor / metabolism * Chromosomal Instability * Chromosomes, Human, Pair 18 ...
Keywords: oncogene; tumour suppressor gene; microsatellite instability; chromosomal instability; DNA methylation; multistep ... 1996) Microsatellite instability in the insulin‐like growth factor II gene in gastrointestinal tumors. Nature Genetics 14(3): ... Each tumour develops its own unique constellation of genetic alterations, and tumours are genetically distinct between tumour ... Tumour Formation: Number of Mutations Required. Lindsay D Butcher, Baylor University, Waco, Texas, USA C Richard Boland, Baylor ...
Even in lamin A/C-positive ovarian cancer, the expression is heterogeneous within the population of tumor cells. In most cancer ... Cancer cells within one tumor or cell line are not uniform in chromosomal number, indicating the presence of chromosomal ... However, lamin A/C-deficient cells exhibit a phenotype of chromosomal numerical instability, though the mechanism was not ... Thompson SL, Bakhoum SF, Compton DA: Mechanisms of chromosomal instability. Curr Biol. 2010, 20: 285-295. 10.1016/j.cub.2010.01 ...
Link unraveled between chromosomal instability and centrosome defects in cancer cells. June 7, 2009 In a new study, Dana-Farber ... Researchers shed light on how tumor cells form. June 21, 2006 MIT cancer researchers have discovered a process that may explain ... A cell that divides into more than two daughter cells undergoes a complex choreography of chromosomal motion that can result in ... "Even though cancer can arise from a set of precise mutations, the majority of malignant tumors possess aneuploid cells, and the ...
2002) The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci USA 99:16226-16231. ... Recombinant Listeria promotes tumor rejection by CD8+ T cell-dependent remodeling of the tumor microenvironment ... 1979) Effects of thymus grafts in nude mice transplated with human malignant tumors. Exp Cell Biol 47:409-429. ... We do not define the biological interaction between the T cell pool and the nascent tumor/infection; however, the concept of ...
Chromosomal Instability Affects the Tumorigenicity of Glioblastoma Tumor-Initiating Cells.. Godek KM, Venere M, Wu Q, Mills KD ... Current review of in vivo GBM rodent models: emphasis on the CNS-1 tumour model. ... Subependymoma and dysembryoplastic neuroepithelial collision tumor in the foramen of Monro: case report. ...
The development of anti-angiogenic drugs would decrease or even arrest tumor growth by restricting the delivery of oxygen and ... either as cytostatic molecules-reducing the proliferation of cancerous cells-or as tumor angiogenesis inhibitors. In this ... Judah Folkman raised the concept of inhibiting tumor angiogenesis for treating solid tumors. ... Chromosomal instability and reactivation of repetitive genomic sequences. . Loss of imprinting Activation of imprinted ...
... homologs of the yeast BRE1 gene serve as tumor suppressors by preventing replication stress and chromosomal instability that ... 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 ...
Replication stress links structural and numerical cancer chromosomal instability. Nature. 2013;494(7438):492-496.. View this ... Tumors were manually measured every 5 days, and mice were sacrificed when tumors reached greater than 15 mm in any direction. ... Failure of origin activation in response to fork stalling leads to chromosomal instability at fragile sites. Mol Cell. 2011;43( ... the expression of KDM5D was found to be lower in CRPC tumors than in hormone-naive primary PC tumors, and CRPC patients with ...
This phenomenon can occur in tumors but also among non-tumor cells. The cell-in-cell phenomenon was first observed 100 years ... Thus, it can also inhibit tumor progression. Studies show that cell-in-cell structure formation is affected by the tumor ... Thus, it can also inhibit tumor progression. Studies show that cell-in-cell structure formation is affected by the tumor ... The cell-in-cell phenomenon was first observed 100 years ago, and it has since been found in a variety of tumor types. Recently ...
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 ...
MutationsGenomicBrain tumorsMicrosatellite instabilityGenetic instabilityTumorigenesisChromosome instabilitySuppressor genesGenesCancersOncogeneMethylationMitoticMetastaticPhenotypeInitiationSuppressorsGenome InstabilityStructural chromosomalMutationWhose tumorsCytogeneticCancerMitosisMechanismsMolecularTumoursSoft tissue tumorsGeneticsDiagnosisPathwayProteinsVitroHeterogeneousPrognosisSpontaneousCellLesionsTP53SurvivalPrimary tumorsOverexpression
- Acting in multiple central processes like double-strand break repair, centrosome replication, and checkpoint control, BRCA1 participates in maintaining genomic integrity and protects the cell against genomic instability. (figshare.com)
- Chromosomal instability (CIN) as part of genomic instability is an inherent characteristic of most solid tumors and is also involved in breast cancer development. (figshare.com)
- The unifying research aim of the department is the understanding of genomic instability in human cancer in order to tailor therapies for cancer patients. (dana-farber.org)
- Kent Mouw, MD, PhD , is using a combination of genomic and functional approaches to study the role of DNA repair pathway alterations in tumor behavior and treatment response. (dana-farber.org)
- 2010) The patterns and dynamics of genomic instability in metastatic pancreatic cancer. (els.net)
- such deficiencies could result in telomere dysfunction and genomic instability. (aacrjournals.org)
- Stoler DL, Chen N, Basik M, Kahlenberg MS, Rodriguez-Bigas MA, Petrelli NJ, Anderson GR (1999) The onset and extent of genomic instability in sporadic colorectal tumor progression. (springer.com)
- Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. (mdpi.com)
- Genomic instability may result in numerous defects like replication errors, telomere dysfunction, epigenetic changes or defective DNA repair as a few examples. (mdpi.com)
- and genomic instability and related molecular, cytogenetic, and chromosomal effects during tumor formation and progression to malignancy. (cancer.gov)
- Genomic instability encompasses a wide spectrum of defects ranging from localized point mutations of one or a few DNA base pairs to large chromosomal rearrangements, such as deletions, amplifications, inversions, translocations, and aneuploidy. (cancer.gov)
- Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology. (biodiscovery.com)
- Comparative Cytogenetic Analysis Of Dog And Human Choroid Plexus Tumors Defines Syntenic Regions Of Genomic Loss. (biodiscovery.com)
- It can inhibit the initiation of tumorigenesis through limiting cytoplasmic damage, genomic instability and inflammation, and the loss of certain autophagy genes can lead to cancer. (biologists.org)
- The research projects proposed in this SPORE address genomic instability in breast cancer. (mskcc.org)
- Our ultimate plan is to exploit tumor-specific vulnerabilities by virtue of their underlying genomic instability. (mskcc.org)
- These profiles of genomic instability have offered novel insights about the drivers of breast cancer development and progression. (mskcc.org)
- In summary, the goals are to take the risks of genomic instability (poor prognosis, rapid development of resistance) and turn genomic instability into an advantage for therapeutic targeting, thereby improving the prognosis for high-risk breast cancers. (mskcc.org)
- In stark contrast to the hematologic malignancies, genomic instability-leading to mutations, deletions, and amplifications-has been proposed to be the molecular basis of carcinomas. (hhmi.org)
- 2000) The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. (springer.com)
- It is known that such defects could lead to genomic instability and tumorigenesis. (biomedsearch.com)
- We have induced tumour development in two ways--by generating genomic instability and the loss of cell polarity. (eurekalert.org)
- A key hallmark of colorectal cancer progression is genomic instability, with chromosomal aneuploidy frequently observed. (cancer.gov)
- These genomic imbalances are maintained when cells metastasize and are conserved in cells lines derived from primary tumors. (cancer.gov)
- Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. (cancer.gov)
- metastatic tumors are typically absent from large-scale genomic cancer surveys such as TCGA. (biomedcentral.com)
- We have proposed a specific signature of progressive genomic changes that leads to full tumor development. (pubmedcentralcanada.ca)
- Five comparative genomic hybridization (CGH) studies and one matrix CGH study confirmed these results and identified common genomic regions of gain and loss in retinoblastoma tumors - . (pubmedcentralcanada.ca)
- We have previously shown that in vitro , Klf4 is required for the prevention of genomic instability ( 10 ). (aacrjournals.org)
- Primary brain tumors, including ependymomas, are a diverse group of diseases that together constitute the most common solid tumor of childhood. (cancer.gov)
- Brain tumors are classified according to histology, but tumor location, extent of spread, molecular features, and age are important factors that affect treatment and prognosis. (cancer.gov)
- The American Academy of Neurology's practice parameters state that prophylactic antiepileptic drugs (AEDs) should not be administered routinely to patients with newly diagnosed brain tumors (standard) and should be discontinued in the first postoperative week in patients who have not experienced a seizure. (medscape.com)
- Postulated mechanisms of action in brain tumors include reduction in vascular permeability, cytotoxic effects on tumors, inhibition of tumor formation, and decreased CSF production. (medscape.com)
- Farrell CJ, Plotkin SR. Genetic causes of brain tumors: neurofibromatosis, tuberous sclerosis, von Hippel-Lindau, and other syndromes. (medscape.com)
- Cellular-telephone use and brain tumors. (medscape.com)
- Of the estimated 17,000 primary brain tumors diagnosed in the United States each year, approximately 60% are gliomas. (medscape.com)
- Cytogenetics and molecular genetics of childhood brain tumors. (springer.com)
- Boland CR and Goel A (2010) Microsatellite instability in colorectal cancer. (els.net)
- The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. (diva-portal.org)
- In the microsatellite instability pathway, what type of mutation is responsible for carcinogenesis in colonic epithelium? (brainscape.com)
- The rate of accumulation of these alterations may be accelerated by a variety of processes that cause genetic instability. (els.net)
- Earlier studies have shown an association between telomere shortening and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and cancer. (mdpi.com)
- Clearly, genetic instability and clonal evolution are driving forces for leukemic transformation. (mdpi.com)
- Overall, our data indicate that despite genetic instability, SHS-survived eMSC do not undergo transformation. (hindawi.com)
- However, chromosomal division abnormalities can cause genetic instability and ultimately induce PTC development [ 4 ]. (hindawi.com)
- The findings 'do not disprove the argument that genetic instability is an inherent feature of tumorigenesis,' the researchers write in Proceedings of the National Academy of Sciences . (genomenewsnetwork.org)
- Instead, they emphasize that, although a subtle instability at the nucleotide level does not play a role in most colorectal cancers, a different form of genetic instability generally occurs in these tumors. (genomenewsnetwork.org)
- The genetic instability in these tumors probably occurred at the chromosomal level rather than the nucleotide level, says Velculescu. (genomenewsnetwork.org)
- Tumor-initiating cells (TIC) that are responsible for tumorigenesis are a source of functional cellular heterogeneity, whereas chromosomal instability (CIN) is a source of karyotypic genetic diversity. (aacrjournals.org)
- Given our current knowledge, the experimental systems already established in X. laevis , and the rapid accumulation of genetic resources for the sister species Silurana (Xenopus) tropicalis , it is our conviction that these species provide an ideal alternative to the murine system for studying tumorigenesis and tumor immunity. (pubmedcentralcanada.ca)
- The availability of these tumor lines as well as genetically defined MHC compatible inbred strains and clones of X. laevis has provided the unique opportunity to study both tumorigenesis and anti-tumor immunity (reviewed in 15 ). (pubmedcentralcanada.ca)
- The results of this study shed further light on the causal relationship between chromosomal instability, loss of epithelial polarity and tumorigenesis and open new avenues for the search of therapeutic targets. (eurekalert.org)
- In vivo, Plk1 overexpression prevents the development of Kras-induced and Her2-induced mammary gland tumors, in the presence of increased rates of chromosome instability. (nih.gov)
- Negative selection and chromosome instability induced by Mad2 overexpression delay breast cancer but facilitate oncogene-independent outgrowth. (dkfz.de)
- Mad2 is a critical mediator of the chromosome instability observed upon Rb and p53 pathway inhibition.Cancer Cell 19(6):701-714. (dkfz.de)
- Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal. (dkfz.de)
- Very CIN-ful: whole chromosome instability promotes tumor suppressor loss of heterozygosity. (dkfz.de)
- The majority of human tumour cells are aneuploid owing to an underlying chromosome instability phenotype. (biologists.org)
- This notion applies particularly to the inactivation of tumor suppressor genes, which requires the loss of both alleles. (pnas.org)
- Cancer is a genetic disease, and occurs through the progressive accumulation of activating alterations to growth‐promoting oncogenes, and inactivating alterations to tumour suppressor genes. (els.net)
- Tumour suppressor genes normally restrain a cell's ability to grow or invade, and inactivation is involved in tumourigenesis. (els.net)
- The reason is that chromosomal material containing important genes can be lost at a high rate. (pnas.org)
- A teleost platyfish-swordtail tumor system has even been used to study the etiology of cancer and reports have demonstrated that neoplasia in these fishes is due to aberrant regulation of certain genes during the multistep process of cancer formation ( 10 ). (pubmedcentralcanada.ca)
- The genes involved in tumour formation are tissue‐specific. (els.net)
- They sequenced regions of 470 genes in normal cells and tumor cells from twelve patients. (genomenewsnetwork.org)
- Many cancers are characterized by chromosomal instability (CIN). (pnas.org)
- Recent studies in mice and humans have stressed the multiple and complex interactions that occur between malignant tumors or cancers and their hosts (reviewed in 16 ). (pubmedcentralcanada.ca)
- Inhibition of tumor angiogenesis based on administration of recombinant humanized antibodies targeting A-VEGF was the first clinically approved angiogenesis-based therapy and has been used in the treatment of several cancers, including breast, colorectal and lung cancers, but the overall effectiveness of this approach is debated [ 3 ]. (mdpi.com)
- Most human cancers contain aneuploid cells, and a significant number of studies have pointed to abnormalities in the regulation of mitosis as a contributing cause of chromosomal instability in tumors ( 1 - 4 ). (asm.org)
- Tumors - in this case metastatic melanomas, or spreading skin cancers - are adept at overcoming their host's natural defenses, in part by emitting agents that disrupt production and operation of the immune system. (healthcanal.com)
- The authors also discuss improved methods to monitor tumor evolution (e.g., liquid biopsies) and the development of more effective strategies for managing and treating cancers (e.g., immunotherapies). (cshlpress.com)
- Polo-like kinase 1 (Plk1) is overexpressed in a wide spectrum of human tumors, being frequently considered as an oncogene and an attractive cancer target. (nih.gov)
- Aurora B is overexpressed in human tumors although whether this kinase may function as an oncogene in vivo is not established. (asm.org)
- It is associated chromosomal aberrations that result in activation of an oncogene on chromosome band 8q12. (bioportfolio.com)
- He has developed a range of methodologies for evaluation of tumor-specific genetic changes, such as mutation and methylation. (dana-farber.org)
- Many inhibitors of DNA methylation as well as of histone methylation, have been successfully tested in preclinical studies and some are currently undergoing evaluation in phase I, II or III clinical trials, either as cytostatic molecules-reducing the proliferation of cancerous cells-or as tumor angiogenesis inhibitors. (mdpi.com)
- Genome Medicine (2018) 10:42 Page 2 of 11 are diagnosed at an early stage , while the 5-year that the circulating tumor DNA (ctDNA) methylation of survival rate decreases to approximately 10% for another ten CpGs could also discriminate HCC patients advanced HCC patients . (deepdyve.com)
- Dysfunctional DNA damage and mitotic spindle checkpoints resulting from these interactions may promote chromosomal instability and leave the hepatocyte unable to control DNA damage caused by oxidative stress mediated by HCV proteins, alcohol, and immune-mediated inflammation. (mysciencework.com)
- Other chromosomal alterations, such as mitotic recombination, can also occur ( 19 - 21 ). (pnas.org)
- Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification. (cancer.gov)
- Mitotic chromosomal instability and cancer: mouse modelling of the human disease. (dkfz.de)
- Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo. (dkfz.de)
- The corresponding phenotype is termed chromosomal instability (CIN) phenotype. (pnas.org)
- In contrast to the familial clustering of gastric cancer, sporadic mismatch repair-deficient gastric tumors present epigenetic silencing of hMLH1 and p16 in the context of a CpG island methylator phenotype (CIMP) [ 10 ]. (intechopen.com)
- Tumor suppressors, chromosomal instability, and hepatitis C vi. (mysciencework.com)
- Tumor suppressors, chromosomal instability, and hepatitis C virus-associated liver cancer. (mysciencework.com)
- Such chromosomal instability may put it at risk of losing genetic material such as tumor suppressors. (bio-medicine.org)
- Placental mosaicism for a subset of a chromosome, a structural chromosomal aberration, is thought to be a very rare finding in chorionic villus samples. (bioportfolio.com)
- 1 The Philadelphia chromosome is defined as translocation of chromosome 9 and 22, 2 and this structural chromosomal change provided new insight into the pathogenesis of leukaemia. (bmj.com)
- A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors. (biodiscovery.com)
- With this assay and mutation assays for the FGFR3 and PIK3CA oncogenes, we screened primary bladder tumors of 257 patients and 184 recurrences from 54 patients. (biomedsearch.com)
- In patients with low-grade NMI-BC, 88% of the primary tumors carried a mutation and 88% of the recurrences were mutant. (biomedsearch.com)
- As such, APC mutation not only compromises tumour suppressor function but may also have oncogenic properties. (biologists.org)
- 16 ][ Level of Evidence: 2Di ] Chromosome 1q gain was recently identified at the time of relapse in three patients with PF-EPN-A whose tumors did not have 1q gain at diagnosis. (cancer.gov)
- In some cases, stereotactic biopsy followed by radiation therapy (eg, for patients with a tumor located in an eloquent area of the brain, patients whose tumors have minimal mass effect, and patients in poor medical condition who cannot undergo general anesthesia). (medscape.com)
- Biologic studies have demonstrated a marked alteration of virulence compared to the parent tumor and striking cytogenetic modifications have been found to exist. (aacrjournals.org)
- Serial examinations over an interval of 22 weekly transplant generations have demonstrated a biologic and cytogenetic instability characterized by, generally, a tendency for return toward control values. (aacrjournals.org)
- The mechanisms by which it causes cancer are unclear, but chronic immune-mediated inflammation and associated oxidative chromosomal DNA damage probably play a role. (mysciencework.com)
- Gerassimos (Mike) Makrigiorgos, PhD , is studying the identification and tracing of tumor signatures in cancer samples. (dana-farber.org)
- Similarly, species among all jawed vertebrate classes develop tumors and cancer ( 7 ) including sharks ( 8 ) that have been mistakenly claimed by some ( 9 ) to be tumor-free. (pubmedcentralcanada.ca)
- We studied early pathological stages (American Joint Committee on Cancer stages I and II (ref. 14 ) of surgically resected HCC with clear microscopic margins (R0 resection) from patients with good liver function (Child-Pugh A). Eight HCC were solitary and one had a concomitant second smaller tumour in the contralateral lobe, treated by intra-operative radiofrequency ablation. (nature.com)
- Researchers at MD Anderson Cancer Center found that somatic copy number alterations are more frequent in normal tissue surrounding tumor than in blood. (genomeweb.com)
- Chromosomal instability (CIN) is a characteristic feature of cancer. (mdpi.com)
- Although microsatellite unstable tumor patients are generally considered to have better prognosis, we found no difference in survival between microsatellite unstable and microsatellite stable (MSS) colorectal cancer patients with similar total CD3 scores. (diva-portal.org)
- Prostate cancer development is often associated with deletion or silencing of tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of the phosphoinositide 3 kinase (PI3K)-Akt pathway, leading to resistance to various therapies in both the preclinical and clinical setting. (aacrjournals.org)
- Thyroid cancer is the most common malignant tumor of the endocrine system and the most common head and neck tumor. (hindawi.com)
- First hypothesized in the early 1900s, there is now compelling evidence for a causal role for chromosomal rearrangements in cancer. (hhmi.org)
- Epithelial tumors (carcinomas) that are much more common and contribute to a relatively large fraction of the morbidity and mortality associated with human cancer comprise less than 1 percent of the known, disease-specific chromosomal rearrangements. (hhmi.org)
- Thus, the identification of recurrent gene rearrangements in common epithelial tumors may have profound implications for the discovery of cancer drugs, as well as for patient treatment. (hhmi.org)
- This process, termed clonal evolution, can lead to the emergence of therapy-resistant tumors and poses a major challenge for cancer eradication efforts. (cshlpress.com)
- In contrast, the intestinal subtype has epithelial features and forms discrete tumor masses similar to colon cancer. (biomedcentral.com)
- Studies of affected HDGC individuals' tumors provide a unique opportunity to determine the essential drivers of diffuse gastric cancer in the context of CDH1 loss of function. (biomedcentral.com)
- In February 2016, the Center started a collaboration with IBM to create a tumor registry matching tumor characteristics and therapeutic responsiveness to genetic profiles among cancer patients. (wikipedia.org)
- Turcot syndrome is the association of colon cancer and CNS tumors, usually medulloblastoma. (upmc.edu)
- Work in our laboratory is supported by grants from American Cancer Society, Children's Tumor foundation, Mark Trauner faculty scholar and Irma T. Hirschl awards. (springer.com)
- Furthermore, tissue microarray of breast cancer patient tumor samples reveals high CDC27 levels compared with nonneoplastic breast tissue and a significant correlation between disease recurrence and CDC27 expression. (aacrjournals.org)
- In addition, high CDC27 expression in breast cancer patient tumor specimens significantly predicts disease recurrence, suggesting a novel role for CDC27 as a predictor of relapse. (aacrjournals.org)
- Chromosomal instability has long been recognized as a hallmark of cancer. (aacrjournals.org)
- In many cancer types, including colorectal cancer, accumulation of DNA damage has been linked to cancer, and genetic deficiencies in DNA damage repair mechanisms are associated with susceptibility to tumor development ( 7 ). (aacrjournals.org)
- Aurora kinase B, one of the three members of the mammalian Aurora kinase family, is the catalytic component of the chromosomal passenger complex, an essential regulator of chromosome segregation in mitosis. (asm.org)
- This protein is found to undergo cell cycle-dependent phosphorylation, which regulates its nuclear matrix and chromatin association, and suggests its involvement in the gene regulation at interphase and chromosomal segregation in mitosis. (cancerindex.org)
- Compelling data suggest that the path to hepatocellular carcinoma in chronic hepatitis C shares some important features with the mechanisms of transformation employed by DNA tumor viruses. (mysciencework.com)
- however, the mechanisms underlying this instability are unknown. (aacrjournals.org)
- Two primary mechanisms of recurrent chromosomal rearrangements have been described. (hhmi.org)
- The researchers have identified two functionally distinct cell populations within the tumour--one that proliferates and ones that does not--upon which internal growth mechanisms depend. (eurekalert.org)
- It is therefore important to understand the mechanisms that drive chromosomal instability. (aacrjournals.org)
- Previous studies showed that KLF4 is a tumor suppressor in the intestinal tract and plays an important role in DNA damage-repair mechanisms. (aacrjournals.org)
- Departmental research is focused on the treatment of tumors and on increasing the understanding of treatments at the molecular and cellular levels. (dana-farber.org)
- D'Andrea's focus is the molecular pathogenesis of the human chromosomal instability syndromes: Fanconi anemia (FA), ataxia-telangiectasia, and Bloom syndrome. (dana-farber.org)
- TP53 (Tumour protein p53 (Li-Fraumeni syndrome) Hybridization with Vysis TP53/CEP 17 probe (Abbott Molecular, US) showing the p53 gene at 17p13.1 (red signals) - Courtesy Adriana Zamecnikova. (atlasgeneticsoncology.org)
- 2006). Thus, there is a dire need to develop novel therapeutic strategies for RTs, preferably based on the understanding of the molecular factors responsible for the genesis, growth, and survival of these tumors. (springer.com)
- Molecular genetics of atypical teratoid/rhabdoid tumor. (springer.com)
- By revealing the molecular subtype of the tumor, it is possible to assess its behavior, the outcome of the patient, and the treatment approach, according to its genetic and epigenetic profile. (intechopen.com)
- Each tumour develops its own unique constellation of genetic alterations, and tumours are genetically distinct between tumour types, and within individual tumours of one type. (els.net)
- In epithelial tumours caused by chromosomal instability or loss of cell polarity, the interaction between two tumour cell populations drives malignant growth," explains Marco Milán , ICREA Research Professor and head of the laboratory. (eurekalert.org)
- We have observed that tumours derived from chromosomal instability are induced by oxidative stress caused by ROS (reactive oxygen species), which triggers JNK. (eurekalert.org)
- An analysis of placental, parental, and cord blood samples indicated that an uptick in chromosomal instability in cleavage-stage in vitro fertilization embryos does not persist after birth. (genomeweb.com)
- Targeting Akt using a novel inhibitor, AZD5363, activates autophagy in resistant prostate cell lines and works synergistically with chloroquine (CHQ) to promote cell death in vitro and in vivo in prostate tumor models. (aacrjournals.org)
- These data suggest that Cdh11 displays tumor suppressor properties in vivo and in vitro in murine retinoblastoma through promotion of cell death. (pubmedcentralcanada.ca)
- Reported cases include calicoblastic neoplasms in coral ( 1 ), tumorigenic germinal cell mediated by Notch in C. elegans ( 2 ), leukemia in bivalve mollusks (oysters) ( 3 , 4 ), intestinal and pigmented tumor in sea urchin ( 5 ) and hepatoma in lampreys ( 6 ). (pubmedcentralcanada.ca)
- The cell-in-cell phenomenon was first observed 100 years ago, and it has since been found in a variety of tumor types. (frontiersin.org)
- Clinical studies have correlated buccal cell changes with malignant tumors, and some oral oncologists have reported that the buccal cell changes are practical biomarkers. (aacrjournals.org)
- The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. (diva-portal.org)
- Thus, overexpression of Aurora B may contribute to tumor formation not only by inducing chromosomal instability but also by suppressing the function of the cell cycle inhibitor p21 Cip1 . (asm.org)
- Blocking autophagy using pharmacologic inhibitors (3-methyladenine, chloroquine, and bafilomycin A) or genetic inhibitors (siRNA targeting Atg3 and Atg7) enhanced cell death induced by Akt inhibitor AZD5363 in these tumor prostate cell lines. (aacrjournals.org)
- Detection of copy number alterations in cell-free tumor DNA from plasma. (biodiscovery.com)
- Cooperation between Cdk4 and p27kip1 in tumor development: a preclinical model to evaluate cell cycle inhibitors with therapeutic activity. (dkfz.de)
- High resolution Chromosomal Microarray Analysis (CMA) enhances the genetic profile of pediatric B-cell Acute Lymphoblastic Leukemia patients. (bioportfolio.com)
- This study is being conducted to develop and evaluate a cell-free fetal DNA test (Ariosa Test) for non-invasive prenatal detection of 22q11.2 chromosomal deletion or duplication. (bioportfolio.com)
- This does not, however, rule out a causal role for gene arrangements in all tumor types, irrespective of their cell of origin. (hhmi.org)
- The scientists observed that the tumour continued to grow in the absence of these two cell types. (eurekalert.org)
- The protein, called 14-3-3, sits at an intersection where it integrates converging signals from within the cell and cues cell shape change and, ultimately, the splitting that allows for normal and abnormal cell growth, such as in tumors. (bio-medicine.org)
- The CDH1 tumor suppressor gene encodes E-cadherin, a transmembrane glycoprotein that mediates calcium-dependent cell-cell adhesion. (biomedcentral.com)
- We present novel data indicating that Cdh11 functions as a tumor suppressor gene in retinoblastoma by facilitating cell death. (pubmedcentralcanada.ca)
- Suppression of cell proliferation and telomerase activity in 4-(hydroxyphenyl)retinamide-treated mammary tumors. (springer.com)
- For a given patient, it is often possible to view in the mouth during a clinical examination normal tissue, premalignant lesions (e.g., leukoplakia), and malignant tumors ( 5 , 6 ). (aacrjournals.org)
- Examples of the schemes that have proven useful are those that have featured technologies that use fluorescence spectroscopy ( 17 ), photodynamic imaging of tumors that have incorporated Photofrin ® ( 18 ), and, in animal studies, multiphoton microscopy of healthy tissue versus malignant lesions as defined in studies of carcinogen-induced tumors ( 19 ). (aacrjournals.org)
- Gastric fundic polyps and duodenal adenomas are also seen, and, in contrast to what is seen in FAP, CHRPE lesions and desmoid tumors rarely have been described in AFAP. (upmc.edu)
- Additionally, in primary tumors p53 expression was obtained by immunohistochemistry. (biomedsearch.com)
- Of primary tumors 64% were mutant for FGFR3, 11% for RAS, 24% for PIK3CA, and 26% for p53. (biomedsearch.com)
- In patients presenting with NMI-BC grade 3 and MI-BC, 33 and 36% of the primary tumors were mutant. (biomedsearch.com)