chromosomal instability

Summary

Summary: An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.

Top Publications

  1. Fungtammasan A, Walsh E, Chiaromonte F, Eckert K, Makova K. A genome-wide analysis of common fragile sites: what features determine chromosomal instability in the human genome?. Genome Res. 2012;22:993-1005 pubmed publisher
    ..Importantly, the genomic features we identified here as significant predictors of fragility allow us to draw valuable inferences on the molecular mechanisms underlying aCFSs...
  2. Giaretti W, Pentenero M, Gandolfo S, Castagnola P. Chromosomal instability, aneuploidy and routine high-resolution DNA content analysis in oral cancer risk evaluation. Future Oncol. 2012;8:1257-71 pubmed publisher
    ..Using high-resolution DNA flow cytometry with fresh/frozen material and the degree of DNA aneuploidy (DNA Index) might improve the prediction of risk of oral cancer development...
  3. Watanabe T, Kobunai T, Yamamoto Y, Matsuda K, Ishihara S, Nozawa K, et al. Chromosomal instability (CIN) phenotype, CIN high or CIN low, predicts survival for colorectal cancer. J Clin Oncol. 2012;30:2256-64 pubmed publisher
    To examine whether chromosomal instability (CIN) phenotype, determined by the severity of CIN, can predict survival for stages II and III colorectal cancer (CRC).
  4. Calado R, Cooper J, Padilla Nash H, Sloand E, Wu C, Scheinberg P, et al. Short telomeres result in chromosomal instability in hematopoietic cells and precede malignant evolution in human aplastic anemia. Leukemia. 2012;26:700-7 pubmed publisher
    In cell and animal models, telomere erosion promotes chromosomal instability via breakage-fusion-bridge cycles, contributing to the early stages of tumorigenesis...
  5. Janssen A, van der Burg M, Szuhai K, Kops G, Medema R. Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations. Science. 2011;333:1895-8 pubmed publisher
    ..Our data show that segregation errors can cause translocations and provide insights into the role of whole-chromosome instability in tumorigenesis...
  6. Bakhoum S, Danilova O, Kaur P, Levy N, Compton D. Chromosomal instability substantiates poor prognosis in patients with diffuse large B-cell lymphoma. Clin Cancer Res. 2011;17:7704-11 pubmed publisher
    The specific role of chromosomal instability (CIN) in tumorigenesis has been a matter of conjecture...
  7. Ling H, Spizzo R, Atlasi Y, Nicoloso M, Shimizu M, Redis R, et al. CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res. 2013;23:1446-61 pubmed publisher
    ..overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated ..
  8. Chen M, Huang J, Deng H, Dong S, Deng W, Tsang S, et al. Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability. BMC Cancer. 2011;11:199 pubmed publisher
    ..In the present study, we aim to investigate the physiological and pathological effect of eIF-5A2 in an eIF-5A2 transgenic mouse model...
  9. Genesca A, Pampalona J, Frias C, Dominguez D, Tusell L. Role of telomere dysfunction in genetic intratumor diversity. Adv Cancer Res. 2011;112:11-41 pubmed publisher
    ..This chromosomal instability most likely occurs early in the development of cancer, and may represent an important step in promoting ..

More Information

Publications62

  1. Solomon D, Kim T, Diaz Martinez L, Fair J, Elkahloun A, Harris B, et al. Mutational inactivation of STAG2 causes aneuploidy in human cancer. Science. 2011;333:1039-43 pubmed publisher
    ..Thus, genetic disruption of cohesin is a cause of aneuploidy in human cancer. ..
  2. Gerling M, Glauben R, Habermann J, Kühl A, Loddenkemper C, Lehr H, et al. Characterization of chromosomal instability in murine colitis-associated colorectal cancer. PLoS ONE. 2011;6:e22114 pubmed publisher
    ..Adequate murine models are thus highly desirable. For human CACs a high frequency of chromosomal instability (CIN) reflected by aneuploidy could be shown, exceeding that of sporadic carcinomas...
  3. Wilkerson M, Yin X, Walter V, Zhao N, Cabanski C, Hayward M, et al. Differential pathogenesis of lung adenocarcinoma subtypes involving sequence mutations, copy number, chromosomal instability, and methylation. PLoS ONE. 2012;7:e36530 pubmed publisher
    ..Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors...
  4. van Pel D, Barrett I, Shimizu Y, Sajesh B, Guppy B, Pfeifer T, et al. An evolutionarily conserved synthetic lethal interaction network identifies FEN1 as a broad-spectrum target for anticancer therapeutic development. PLoS Genet. 2013;9:e1003254 pubmed publisher
  5. Gao Y, Li T, Chang Y, Wang Y, Zhang W, Li W, et al. Cdk1-phosphorylated CUEDC2 promotes spindle checkpoint inactivation and chromosomal instability. Nat Cell Biol. 2011;13:924-33 pubmed publisher
    Aneuploidy and chromosomal instability are major characteristics of human cancer...
  6. Dai C, Sun F, Zhu C, Hu X. Tumor environmental factors glucose deprivation and lactic acidosis induce mitotic chromosomal instability--an implication in aneuploid human tumors. PLoS ONE. 2013;8:e63054 pubmed publisher
    Mitotic chromosomal instability (CIN) plays important roles in tumor progression, but what causes CIN is incompletely understood...
  7. Heselmeyer Haddad K, Berroa Garcia L, Bradley A, Ortiz Melendez C, Lee W, Christensen R, et al. Single-cell genetic analysis of ductal carcinoma in situ and invasive breast cancer reveals enormous tumor heterogeneity yet conserved genomic imbalances and gain of MYC during progression. Am J Pathol. 2012;181:1807-22 pubmed publisher
    ..The DCIS had a lower degree of chromosomal instability than the IDC...
  8. Hu L, Liu X, Chervona Y, Yang F, Tang M, Darzynkiewicz Z, et al. Chromium induces chromosomal instability, which is partly due to deregulation of BubR1 and Emi1, two APC/C inhibitors. Cell Cycle. 2011;10:2373-9 pubmed
    ..Combined, these results suggest that Cr(VI)-induced chromosomal instability is partly due to a perturbation of APC/C activities, leading to chromosomal instability.
  9. Chernikova S, Razorenova O, Higgins J, Sishc B, Nicolau M, Dorth J, et al. Deficiency in mammalian histone H2B ubiquitin ligase Bre1 (Rnf20/Rnf40) leads to replication stress and chromosomal instability. Cancer Res. 2012;72:2111-9 pubmed publisher
  10. Frankenberg Schwager M, Gregus A. Chromosomal instability induced by mammography X-rays in primary human fibroblasts from BRCA1 and BRCA2 mutation carriers. Int J Radiat Biol. 2012;88:846-57 pubmed publisher
  11. Hell M, Thoma C, Fankhauser N, Christinat Y, Weber T, Krek W. miR-28-5p promotes chromosomal instability in VHL-associated cancers by inhibiting Mad2 translation. Cancer Res. 2014;74:2432-43 pubmed publisher
    b>Chromosomal instability enables tumor development, enabled in part by aberrant expression of the mitotic checkpoint protein Mad2...
  12. Stirling P, Crisp M, Basrai M, Tucker C, Dunham M, Spencer F, et al. Mutability and mutational spectrum of chromosome transmission fidelity genes. Chromosoma. 2012;121:263-75 pubmed publisher
    ..These observations inform our understanding of recurring CIN mutations in human cancers where presumably random mutations are responsible for initiating the frequently observed CIN phenotype of tumors...
  13. Itan E, Tannenbaum E. Effect of chromosomal instability on the mutation-selection balance in unicellular populations. PLoS ONE. 2012;7:e26513 pubmed publisher
    ..model describing the evolutionary dynamics of a unicellular, asexually replicating population exhibiting chromosomal instability. Chromosomal instability is a form of genetic instability characterized by the gain or loss of entire ..
  14. Bond C, Umapathy A, Buttenshaw R, Wockner L, Leggett B, Whitehall V. Chromosomal instability in BRAF mutant, microsatellite stable colorectal cancers. PLoS ONE. 2012;7:e47483 pubmed publisher
    ..BRAF wild type cancers are typically microsatellite stable (MSS) and instead acquire chromosomal instability (CIN). In these cancers, CIN is associated with a poor outcome...
  15. Yang H, Kim T, Song S, Shrinath N, Park R, Kalamarides M, et al. Alternative splicing of CHEK2 and codeletion with NF2 promote chromosomal instability in meningioma. Neoplasia. 2012;14:20-8 pubmed
    ..during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with ..
  16. Gordon D, Resio B, Pellman D. Causes and consequences of aneuploidy in cancer. Nat Rev Genet. 2012;13:189-203 pubmed publisher
    ..We also explore the role of aneuploidy in cellular transformation and discuss the possibility of developing aneuploidy-specific therapies...
  17. Ryan S, Britigan E, Zasadil L, Witte K, Audhya A, Roopra A, et al. Up-regulation of the mitotic checkpoint component Mad1 causes chromosomal instability and resistance to microtubule poisons. Proc Natl Acad Sci U S A. 2012;109:E2205-14 pubmed publisher
    The mitotic checkpoint is the major cell cycle checkpoint acting during mitosis to prevent aneuploidy and chromosomal instability, which are hallmarks of tumor cells...
  18. Chang L, Guo R, Huang Q, Yen Y. Chromosomal instability triggered by Rrm2b loss leads to IL-6 secretion and plasmacytic neoplasms. Cell Rep. 2013;3:1389-97 pubmed publisher
    ..Thus, Rrm2b plays a crucial role in maintaining chromosomal stability and preventing chronic-inflammation-associated tumorigenesis...
  19. Pentenero M, Donadini A, Di Nallo E, Maffei M, Marino R, Familiari U, et al. Distinctive chromosomal instability patterns in oral verrucous and squamous cell carcinomas detected by high-resolution DNA flow cytometry. Cancer. 2011;117:5052-7 pubmed publisher
    ..Because chromosomal instability (CIN) in solid tumors is indicative of prognosis, this study investigated whether OVCs and OSCCs were ..
  20. Begus Nahrmann Y, Hartmann D, Kraus J, Eshraghi P, Scheffold A, Grieb M, et al. Transient telomere dysfunction induces chromosomal instability and promotes carcinogenesis. J Clin Invest. 2012;122:2283-8 pubmed publisher
    ..A current hypothesis suggests that telomere dysfunction increases tumor initiation by induction of chromosomal instability, but that initiated tumors need to reactivate telomerase for genome stabilization and tumor progression...
  21. Ren J, Wang Y, Gao Y, Mehta S, Lee C. FAT10 mediates the effect of TNF-? in inducing chromosomal instability. J Cell Sci. 2011;124:3665-75 pubmed publisher
    ..Previously, we reported that high levels of FAT10 led to chromosomal instability that is mediated by an abbreviated mitotic phase...
  22. Singh D, Chan J, Zoppoli P, Niola F, Sullivan R, Castaño A, et al. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science. 2012;337:1231-5 pubmed publisher
    ..FGFR-TACC fusions could potentially identify a subset of GBM patients who would benefit from targeted FGFR kinase inhibition...
  23. Martinez A C, van Wely K. Centromere fission, not telomere erosion, triggers chromosomal instability in human carcinomas. Carcinogenesis. 2011;32:796-803 pubmed publisher
    ..The three main pathways of chromosomal instability (CIN) proposed until now (random breakage, telomere fusion and centromere fission) are largely based on ..
  24. Hamada M, Malureanu L, Wijshake T, Zhou W, van Deursen J. Reprogramming to pluripotency can conceal somatic cell chromosomal instability. PLoS Genet. 2012;8:e1002913 pubmed publisher
    ..Thus, karyotypic analysis of somatic cells of origin in addition to iPSC lines is necessary for safe application of reprogramming technology...
  25. Takahashi Y, Hori T, Cooper T, Liao J, Desai N, Serfass J, et al. Bif-1 haploinsufficiency promotes chromosomal instability and accelerates Myc-driven lymphomagenesis via suppression of mitophagy. Blood. 2013;121:1622-32 pubmed publisher
    ..endophilin protein, is a haploinsufficient tumor suppressor that plays a key role in the prevention of chromosomal instability and suppresses the acquisition of apoptosis resistance during Myc-driven lymphomagenesis...
  26. Szasz A, Li Q, Eklund A, Sztupinszki Z, Rowan A, Tokes A, et al. The CIN4 chromosomal instability qPCR classifier defines tumor aneuploidy and stratifies outcome in grade 2 breast cancer. PLoS ONE. 2013;8:e56707 pubmed publisher
    Quantifying chromosomal instability (CIN) has both prognostic and predictive clinical utility in breast cancer...
  27. Lushnikova T, Bouska A, Odvody J, Dupont W, Eischen C. Aging mice have increased chromosome instability that is exacerbated by elevated Mdm2 expression. Oncogene. 2011;30:4622-31 pubmed publisher
  28. Ayuda Dur n P, Devesa F, Gomes F, Sequeira Mendes J, Ávila Zarza C, G mez M, et al. The CDK regulators Cdh1 and Sic1 promote efficient usage of DNA replication origins to prevent chromosomal instability at a chromosome arm. Nucleic Acids Res. 2014;42:7057-68 pubmed publisher
    ..We therefore propose that CDK deregulation in G1 phase compromises origin redundancy by decreasing the number of active and dormant origins, leading to origin shortage and increased chromosome instability...
  29. Chakraborty S, Stark J, Sun C, Modi H, Chen W, O Connor T, et al. Chronic myelogenous leukemia stem and progenitor cells demonstrate chromosomal instability related to repeated breakage-fusion-bridge cycles mediated by increased nonhomologous end joining. Blood. 2012;119:6187-97 pubmed publisher
    ..These studies reveal a previously unrecognized mechanism of chromosomal instability in leukemia progenitors because of continued generation of unstable chromosomal lesions through repeated ..
  30. BURRELL R, McClelland S, Endesfelder D, Groth P, Weller M, Shaikh N, et al. Replication stress links structural and numerical cancer chromosomal instability. Nature. 2013;494:492-496 pubmed publisher
    Cancer chromosomal instability (CIN) results in an increased rate of change of chromosome number and structure and generates intratumour heterogeneity...
  31. Brevini T, Pennarossa G, Maffei S, Tettamanti G, Vanelli A, Isaac S, et al. Centrosome amplification and chromosomal instability in human and animal parthenogenetic cell lines. Stem Cell Rev. 2012;8:1076-87 pubmed publisher
  32. Casimiro M, Pestell R. Cyclin d1 induces chromosomal instability. Oncotarget. 2012;3:224-5 pubmed
    ..There is increasing interest in employing drugs in the clinic that exploit CIN in tumors. The high CIN expression index in luminal B breast cancer provides a basis for using Cdk and CIN inhibitors as a targeted therapeutic approach...
  33. Bakhoum S, Compton D. Chromosomal instability and cancer: a complex relationship with therapeutic potential. J Clin Invest. 2012;122:1138-43 pubmed publisher
    b>Chromosomal instability (CIN) is a hallmark of human neoplasms. Despite its widespread prevalence, knowledge of the mechanisms and contributions of CIN in cancer has been elusive...
  34. Zhang H, Chen X, Jin Y, Liu B, Zhou L. Overexpression of Aurora-A promotes laryngeal cancer progression by enhancing invasive ability and chromosomal instability. Eur Arch Otorhinolaryngol. 2012;269:607-14 pubmed publisher
    ..laryngeal squamous cell carcinoma (LSCC) and to explore the effects of Aurora-A silencing on invasion and chromosomal instability in laryngeal cancer HEp-2 cells...
  35. Zhang H, Chen X, Liu B, Zhou L. Effects of stable knockdown of Aurora kinase A on proliferation, migration, chromosomal instability, and expression of focal adhesion kinase and matrix metalloproteinase-2 in HEp-2 cells. Mol Cell Biochem. 2011;357:95-106 pubmed publisher
    ..Knockdown of AURKA caused delayed entry into mitosis after treatment with nocodazole, reduced chromosomal instability, and decreased expression of focal adhesion kinase (FAK), phosphorylated FAK, and matrix ..
  36. Sperka T, Song Z, Morita Y, Nalapareddy K, Guachalla L, Lechel A, et al. Puma and p21 represent cooperating checkpoints limiting self-renewal and chromosomal instability of somatic stem cells in response to telomere dysfunction. Nat Cell Biol. 2011;14:73-9 pubmed publisher
    ..and cell-cycle arrest act in cooperating checkpoints limiting tissue maintenance and evolution of chromosomal instability at stem- and progenitor-cell levels in response to telomere dysfunction...
  37. Roylance R, Endesfelder D, Gorman P, BURRELL R, Sander J, Tomlinson I, et al. Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer. Cancer Epidemiol Biomarkers Prev. 2011;20:2183-94 pubmed publisher
    b>Chromosomal instability (CIN) is thought to be associated with poor prognosis in solid tumors; however, evidence from preclinical and mouse tumor models suggest that CIN may paradoxically enhance or impair cancer cell fitness...
  38. Focken T, Steinemann D, Skawran B, Hofmann W, Ahrens P, Arnold N, et al. Human BRCA1-associated breast cancer: no increase in numerical chromosomal instability compared to sporadic tumors. Cytogenet Genome Res. 2011;135:84-92 pubmed publisher
    ..b>Chromosomal instability (CIN) as part of genomic instability is an inherent characteristic of most solid tumors and is also ..
  39. Stirling P, Bloom M, Solanki Patil T, Smith S, Sipahimalani P, Li Z, et al. The complete spectrum of yeast chromosome instability genes identifies candidate CIN cancer genes and functional roles for ASTRA complex components. PLoS Genet. 2011;7:e1002057 pubmed publisher
    ..Overall, the CIN gene spectrum reveals new chromosome biology and will help us to understand CIN phenotypes in human disease...
  40. Murnane J. Telomere dysfunction and chromosome instability. Mutat Res. 2012;730:28-36 pubmed publisher
    ..Knowledge concerning the factors promoting telomere loss and its consequences is therefore important for understanding chromosome instability in human cancer...
  41. Sir J, Putz M, Daly O, Morrison C, Dunning M, Kilmartin J, et al. Loss of centrioles causes chromosomal instability in vertebrate somatic cells. J Cell Biol. 2013;203:747-56 pubmed publisher
    ..Cells without centrioles exhibited both a delay in bipolar spindle assembly and a high rate of chromosomal instability. Collectively, our results expose a vital role for centrosomes in establishing a mitotic spindle geometry ..
  42. Milosevic Djordjevic O, Stošić I, Grujicic D, Bankovic D, Arsenijevic S. Cervical precancerous lesions--chromosomal instability in peripheral blood lymphocytes in relation to lesion stage, age and smoking habits. Acta Obstet Gynecol Scand. 2011;90:1082-7 pubmed publisher
    ..To evaluate chromosomal damage in peripheral blood lymphocytes (PBL) of patients newly diagnosed with cervical precancerous lesions with respect to age, smoking habits, miscarriages, abortions and lesion stage...
  43. Ozeri Galai E, Lebofsky R, Rahat A, Bester A, Bensimon A, Kerem B. Failure of origin activation in response to fork stalling leads to chromosomal instability at fragile sites. Mol Cell. 2011;43:122-31 pubmed publisher
    Perturbed DNA replication in early stages of cancer development induces chromosomal instability preferentially at fragile sites. However, the molecular basis for this instability is unknown...
  44. Zhang Y, van Deursen J, Galardy P. Overexpression of ubiquitin specific protease 44 (USP44) induces chromosomal instability and is frequently observed in human T-cell leukemia. PLoS ONE. 2011;6:e23389 pubmed publisher
    ..These data are consistent with an important role for USP44 in regulating Cdc20-APC/C activity and suggest that high levels of this enzyme may contribute to the pathogenesis of T-ALL...
  45. Casimiro M, Crosariol M, Loro E, Ertel A, Yu Z, Dampier W, et al. ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice. J Clin Invest. 2012;122:833-43 pubmed publisher
    b>Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood...
  46. Pampalona J, Frias C, Genesca A, Tusell L. Progressive telomere dysfunction causes cytokinesis failure and leads to the accumulation of polyploid cells. PLoS Genet. 2012;8:e1002679 pubmed publisher
    ..of carcinogenesis, we investigated whether there is a connection between these two important promoters of chromosomal instability. We report that human mammary epithelial cells exhibiting progressive telomere dysfunction, in a pRb ..
  47. McGranahan N, BURRELL R, Endesfelder D, Novelli M, Swanton C. Cancer chromosomal instability: therapeutic and diagnostic challenges. EMBO Rep. 2012;13:528-38 pubmed publisher
    b>Chromosomal instability (CIN)-which is a high rate of loss or gain of whole or parts of chromosomes-is a characteristic of most human cancers and a cause of tumour aneuploidy and intra-tumour heterogeneity...
  48. Kim T, Ko J, Hu L, Kim S, Bishop A, Vijg J, et al. RAD51 mutants cause replication defects and chromosomal instability. Mol Cell Biol. 2012;32:3663-80 pubmed publisher
    ..We found very low levels of mutant protein present at these sites compared to normal protein, suggesting that low levels of mutant protein were sufficient for disruption of RAD51 activity and generation of chromosomal rearrangements...
  49. Zasadil L, Britigan E, Weaver B. 2n or not 2n: Aneuploidy, polyploidy and chromosomal instability in primary and tumor cells. Semin Cell Dev Biol. 2013;24:370-9 pubmed publisher
    ..aneuploid karyotype, while others consistently missegregate chromosomes over multiple divisions due to chromosomal instability (CIN). Both aneuploidy and CIN serve as markers of poor prognosis in diverse human cancers...
  50. Pfau S, Amon A. Chromosomal instability and aneuploidy in cancer: from yeast to man. EMBO Rep. 2012;13:515-27 pubmed publisher
    ..Several model systems have been developed to study the role of chromosomal instability and aneuploidy in tumorigenesis...
  51. Mishra A, Liu S, Sams G, Curphey D, Santhanam R, Rush L, et al. Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia through chromosomal instability and DNA hypermethylation. Cancer Cell. 2012;22:645-55 pubmed publisher
    ..Drug targeting that reverses miR-29b repression cures otherwise fatal LGL leukemia. We show how excessive IL-15 initiates cancer and demonstrate effective drug targeting for potential therapy of human LGL leukemia...
  52. Carvalho B, Sillars Hardebol A, Postma C, Mongera S, Terhaar sive Droste J, Obulkasim A, et al. Colorectal adenoma to carcinoma progression is accompanied by changes in gene expression associated with ageing, chromosomal instability, and fatty acid metabolism. Cell Oncol (Dordr). 2012;35:53-63 pubmed publisher
    ..It is estimated that only about 5% of adenomas do progress to a carcinoma...
  53. Krem M, Luo P, Ing B, Horwitz M. The kelch protein KLHDC8B guards against mitotic errors, centrosomal amplification, and chromosomal instability. J Biol Chem. 2012;287:39083-93 pubmed publisher
    The malignant cell in classical Hodgkin lymphoma (HL) is the binucleated giant Reed-Sternberg cell. Chromosomal instability and mitotic errors may contribute to HL pathogenesis; one potential mitotic regulator is the kelch protein ..