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. ncbi Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
    Sunil R Hingorani
    Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Cell 7:469-83. 2005
  2. pmc A mechanism linking extra centrosomes to chromosomal instability
    Neil J Ganem
    Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 460:278-82. 2009
  3. ncbi Replication stress links structural and numerical cancer chromosomal instability
    REBECCA A BURRELL
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Nature 494:492-6. 2013
  4. ncbi Shelterin: the protein complex that shapes and safeguards human telomeres
    Titia de Lange
    The Rockefeller University, New York, New York 10021, USA
    Genes Dev 19:2100-10. 2005
  5. ncbi A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers
    Scott L Carter
    Children s Hospital Informatics Program at the Harvard MIT Division of Health Sciences and Technology Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 38:1043-8. 2006
  6. pmc Differential pathogenesis of lung adenocarcinoma subtypes involving sequence mutations, copy number, chromosomal instability, and methylation
    Matthew D Wilkerson
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
    PLoS ONE 7:e36530. 2012
  7. ncbi Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations
    Aniek Janssen
    Department of Medical Oncology and Cancer Genomics Center, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands
    Science 333:1895-8. 2011
  8. pmc A genome-wide analysis of common fragile sites: what features determine chromosomal instability in the human genome?
    Arkarachai Fungtammasan
    The Integrative Biosciences Graduate Program, Bioinformatics and Genomics Option, Pennsylvania State University, University Park, PA 16802, USA
    Genome Res 22:993-1005. 2012
  9. pmc Autophagy suppresses tumor progression by limiting chromosomal instability
    Robin Mathew
    University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Genes Dev 21:1367-81. 2007
  10. ncbi Aneuploidy and cancer
    Harith Rajagopalan
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, Maryland 21231, USA
    Nature 432:338-41. 2004

Detail Information

Publications348 found, 100 shown here

  1. ncbi Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
    Sunil R Hingorani
    Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Cell 7:469-83. 2005
    ..These findings have clear implications for understanding mechanisms of disease pathogenesis, and for the development of detection and targeted treatment strategies...
  2. pmc A mechanism linking extra centrosomes to chromosomal instability
    Neil J Ganem
    Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 460:278-82. 2009
    b>Chromosomal instability (CIN) is a hallmark of many tumours and correlates with the presence of extra centrosomes. However, a direct mechanistic link between extra centrosomes and CIN has not been established...
  3. ncbi Replication stress links structural and numerical cancer chromosomal instability
    REBECCA A BURRELL
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Nature 494:492-6. 2013
    Cancer chromosomal instability (CIN) results in an increased rate of change of chromosome number and structure and generates intratumour heterogeneity...
  4. ncbi Shelterin: the protein complex that shapes and safeguards human telomeres
    Titia de Lange
    The Rockefeller University, New York, New York 10021, USA
    Genes Dev 19:2100-10. 2005
    ..Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1...
  5. ncbi A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers
    Scott L Carter
    Children s Hospital Informatics Program at the Harvard MIT Division of Health Sciences and Technology Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 38:1043-8. 2006
    ..We identified a signature of chromosomal instability from specific genes whose expression was consistently correlated with total functional aneuploidy in ..
  6. pmc Differential pathogenesis of lung adenocarcinoma subtypes involving sequence mutations, copy number, chromosomal instability, and methylation
    Matthew D Wilkerson
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
    PLoS ONE 7:e36530. 2012
    ..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...
  7. ncbi Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations
    Aniek Janssen
    Department of Medical Oncology and Cancer Genomics Center, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands
    Science 333:1895-8. 2011
    ..Our data show that segregation errors can cause translocations and provide insights into the role of whole-chromosome instability in tumorigenesis...
  8. pmc A genome-wide analysis of common fragile sites: what features determine chromosomal instability in the human genome?
    Arkarachai Fungtammasan
    The Integrative Biosciences Graduate Program, Bioinformatics and Genomics Option, Pennsylvania State University, University Park, PA 16802, USA
    Genome Res 22:993-1005. 2012
    ..Importantly, the genomic features we identified here as significant predictors of fragility allow us to draw valuable inferences on the molecular mechanisms underlying aCFSs...
  9. pmc Autophagy suppresses tumor progression by limiting chromosomal instability
    Robin Mathew
    University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Genes Dev 21:1367-81. 2007
    ..Identification of this novel role of autophagy may be important for rational chemotherapy and therapeutic exploitation of autophagy inducers as potential chemopreventive agents...
  10. ncbi Aneuploidy and cancer
    Harith Rajagopalan
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, Maryland 21231, USA
    Nature 432:338-41. 2004
    ..of evidence suggests that aneuploidy is often caused by a particular type of genetic instability, called chromosomal instability, which may reflect defects in mitotic segregation in cancer cells...
  11. pmc Cancer chromosomal instability: therapeutic and diagnostic challenges
    Nicholas McGranahan
    Translational Cancer Therapeutics Laboratory, CRUK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    EMBO Rep 13:528-38. 2012
    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...
  12. pmc Chromosomal instability confers intrinsic multidrug resistance
    Alvin J X Lee
    Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, London, United Kingdom
    Cancer Res 71:1858-70. 2011
    ..Spontaneous chromosome missegregation events in aneuploid cells promote chromosomal instability (CIN) that may contribute to the acquisition of multidrug resistance in vitro and heighten risk for tumor ..
  13. pmc Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells
    William T Silkworth
    Virginia Tech, Department of Biological Sciences, Blacksburg, VA, USA
    PLoS ONE 4:e6564. 2009
    ..We propose this spindle pole coalescence mechanism as a major contributor to chromosome instability in cancer cells...
  14. pmc Mechanisms of chromosomal instability
    Sarah L Thompson
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Curr Biol 20:R285-95. 2010
    ..of the haploid number, and many frequently mis-segregate whole chromosomes in a phenomenon called chromosomal instability (CIN)...
  15. pmc Paradoxical relationship between chromosomal instability and survival outcome in cancer
    Nicolai J Birkbak
    Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark
    Cancer Res 71:3447-52. 2011
    b>Chromosomal instability (CIN) is associated with poor prognosis in human cancer. However, in certain animal tumor models elevated CIN negatively impacts upon organism fitness, and is poorly tolerated by cancer cells...
  16. pmc Chromosomal instability and aneuploidy in cancer: from yeast to man
    Sarah J Pfau
    David H Koch Institute for Integrative Cancer Research and Howard Hughes Medical Institute, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA
    EMBO Rep 13:515-27. 2012
    ..Several model systems have been developed to study the role of chromosomal instability and aneuploidy in tumorigenesis...
  17. pmc Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers
    Thomas D Barber
    The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 105:3443-8. 2008
    ..We then demonstrated that down-regulation of such homologs resulted in chromosomal instability and chromatid cohesion defects in human cells...
  18. ncbi Patterns and incidence of chromosomal instability and their prognostic relevance in breast cancer subtypes
    Marcel Smid
    Department of Medical Oncology, Josephine Nefkens Institute, Erasmus MC, Dr, Rotterdam, The Netherlands
    Breast Cancer Res Treat 128:23-30. 2011
    One of the hallmarks of human solid tumors is chromosomal instability (CIN). We studied global patterns as well as individual levels of CIN and determined the prognostic relevance among breast cancer subtypes...
  19. pmc Up-regulation of the mitotic checkpoint component Mad1 causes chromosomal instability and resistance to microtubule poisons
    Sean D Ryan
    Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI 53705, USA
    Proc Natl Acad Sci U S A 109:E2205-14. 2012
    The mitotic checkpoint is the major cell cycle checkpoint acting during mitosis to prevent aneuploidy and chromosomal instability, which are hallmarks of tumor cells...
  20. pmc Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer
    Michal Sheffer
    Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel
    Proc Natl Acad Sci U S A 106:7131-6. 2009
    ..Annotation analysis reveals that the oxidative phosphorylation pathway shows a strong tendency for decreased expression in the samples characterized by poor prognosis...
  21. ncbi Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites
    Francene J Lemoine
    Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cell 120:587-98. 2005
    ..We demonstrate that this pair of Ty elements constitutes a preferred site for double-strand DNA breaks when DNA replication is compromised, analogous to the fragile sites observed in mammalian chromosomes...
  22. pmc The complete spectrum of yeast chromosome instability genes identifies candidate CIN cancer genes and functional roles for ASTRA complex components
    Peter C Stirling
    Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
    PLoS Genet 7:e1002057. 2011
    ..Overall, the CIN gene spectrum reveals new chromosome biology and will help us to understand CIN phenotypes in human disease...
  23. ncbi Failure of origin activation in response to fork stalling leads to chromosomal instability at fragile sites
    Efrat Ozeri-Galai
    Department of Genetics, The Life Sciences Institute, Edmond J Safra Campus, The Hebrew University, Jerusalem 91904, Israel
    Mol Cell 43:122-31. 2011
    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...
  24. pmc Chromosomal instability determines taxane response
    Charles Swanton
    Cancer Research UK, London Research Institute, London WC2A 3PX, United Kingdom
    Proc Natl Acad Sci U S A 106:8671-6. 2009
    ..cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN)...
  25. pmc Proliferation of aneuploid human cells is limited by a p53-dependent mechanism
    Sarah L Thompson
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    J Cell Biol 188:369-81. 2010
    ..that aneuploidy is the consequence of an elevated rate of chromosome missegregation in a process called chromosomal instability (CIN)...
  26. ncbi Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis
    A Walther
    Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, UK
    Gut 57:941-50. 2008
    ..Recently, however, data have suggested this is secondary to the effects of ploidy/chromosomal instability (CIN)...
  27. pmc Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer
    Rebecca Roylance
    Cancer Research UK, London Research Institute, London, United Kingdom
    Cancer Epidemiol Biomarkers Prev 20:2183-94. 2011
    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...
  28. ncbi The consequences of tetraploidy and aneuploidy
    Zuzana Storchova
    Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    J Cell Sci 121:3859-66. 2008
    ..Tetraploidization can initiate chromosomal instability (CIN), probably owing to supernumerary centrosomes and the doubled chromosome mass...
  29. ncbi Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myélom
    Olivier Decaux
    L Institut National de la Santé et de la Recherche Médicale, U892, University of Nantes, University, Hospital, Hematology Laboratory, Nantes, France
    J Clin Oncol 26:4798-805. 2008
    ..We used gene expression profiles of myeloma cells obtained at diagnosis to identify broadly applicable prognostic markers...
  30. pmc Chromosomal instability substantiates poor prognosis in patients with diffuse large B-cell lymphoma
    Samuel F Bakhoum
    Department of Biochemistry The Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03755, USA
    Clin Cancer Res 17:7704-11. 2011
    The specific role of chromosomal instability (CIN) in tumorigenesis has been a matter of conjecture...
  31. pmc Deviant kinetochore microtubule dynamics underlie chromosomal instability
    Samuel F Bakhoum
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Curr Biol 19:1937-42. 2009
    The persistent malattachment of microtubules to chromosomes at kinetochores is a major mechanism of chromosomal instability (CIN) [1, 2]...
  32. ncbi Transforming growth factor beta1 promotes chromosomal instability in human papillomavirus 16 E6E7-infected cervical epithelial cells
    Wen Deng
    Department of Anatomy, The University of Hong Kong, Hong Kong, SAR, China
    Cancer Res 68:7200-9. 2008
    ..mainly human papillomavirus (HPV)-16 and HPV18] oncogenes E6 and E7 and characteristically exhibits chromosomal instability. However, the mechanisms underlying chromosomal instability in cervical cancer are still not fully ..
  33. ncbi Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin
    Shigehiro A Kawashima
    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113 0032, Japan
    Science 327:172-7. 2010
    ..Impairment of Bub1 in humans may lead to chromosomal instability (CIN) or tumorigenesis. Yet, the primary cellular substrate of Bub1 has remained elusive...
  34. pmc Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor cells
    Aniek Janssen
    Department of Medical Oncology, Cancer Genomics Center, UMC Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
    Proc Natl Acad Sci U S A 106:19108-13. 2009
    ..Thus, targeting the mitotic checkpoint and chromosome alignment simultaneously may selectively kill tumor cells by enhancing chromosome mis-segregations...
  35. pmc Toward a comprehensive temperature-sensitive mutant repository of the essential genes of Saccharomyces cerevisiae
    Shay Ben-Aroya
    Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
    Mol Cell 30:248-58. 2008
    ..The importance of this collection is demonstrated by biochemical and genetic screens that reveal essential genes involved in RNA processing and maintenance of chromosomal stability...
  36. pmc Loss of pRB causes centromere dysfunction and chromosomal instability
    Amity L Manning
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Genes Dev 24:1364-76. 2010
    ..These observations explain an important consequence of RB1 inactivation, and suggest that subtle defects in centromere function are a frequent source of merotely and CIN in cancer...
  37. pmc Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis
    Andrew J Holland
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, San Diego, La Jolla, California 92093 0670, USA
    Nat Rev Mol Cell Biol 10:478-87. 2009
    ..A clearer understanding of the tumour suppressive function of aneuploidy might reveal new avenues for anticancer therapy...
  38. pmc The nature of telomere fusion and a definition of the critical telomere length in human cells
    Rebecca Capper
    Department of Pathology, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom
    Genes Dev 21:2495-508. 2007
    ..stable length in normal human cells, a subset of stochastically shortened telomeres can potentially cause chromosomal instability. Telomere fusion was accompanied by the deletion of one or both telomeres extending several kilobases ..
  39. pmc The chromosomal instability pathway in colon cancer
    Maria S Pino
    Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Gastroenterology 138:2059-72. 2010
    ..in tumor development and there are at least 3 distinct pathways in colorectal cancer pathogenesis: the chromosomal instability (CIN), microsatellite instability, and CpG island methylator phenotype pathways...
  40. ncbi Twist overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer
    Yelena Mironchik
    Department of Radiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA
    Cancer Res 65:10801-9. 2005
    ..results show that Twist overexpression in breast cancer cells can induce angiogenesis, correlates with chromosomal instability, and promotes an epithelial-mesenchymal-like transition that is pivotal for the transformation into an ..
  41. pmc CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer
    Hui Ling
    Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Genome Res 23:1446-61. 2013
    ..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 ..
  42. pmc Transient telomere dysfunction induces chromosomal instability and promotes carcinogenesis
    Yvonne Begus-Nahrmann
    Institute for Molecular Oncology, University Medical Center, Gottingen, Germany
    J Clin Invest 122:2283-8. 2012
    ..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...
  43. ncbi Chromosomal instability in microsatellite-unstable and stable colon cancer
    Karolin Trautmann
    Comprehensive Cancer Center, Department of Medicine, University of California San Francisco, San Francisco, California 94143 0808, USA
    Clin Cancer Res 12:6379-85. 2006
    ..in colon cancer can be divided into at least two major types, microsatellite instability (MSI) or chromosomal instability (CIN)...
  44. pmc Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal
    Rocio Sotillo
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 464:436-40. 2010
    ..However, there has been no systematic exploration of whether chromosomal instability generated as a result of deregulation of the mitotic checkpoint pathway, a frequent characteristic of ..
  45. pmc Whole chromosome instability caused by Bub1 insufficiency drives tumorigenesis through tumor suppressor gene loss of heterozygosity
    Darren J Baker
    Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Cancer Cell 16:475-86. 2009
    ..Thus, Bub1 insufficiency can drive tumor formation through tumor suppressor gene loss of heterozygosity, but only in restricted genetic and cellular contexts...
  46. ncbi Mitochondrial oxidative stress causes chromosomal instability of mouse embryonic fibroblasts
    E Samper
    Buck Institute for Age Research, Novato, CA 94945, USA
    Aging Cell 2:277-85. 2003
    ..Our results predict that endogenous mitochondrial oxidative stress can induce genomic instability, and therefore may have a profound effect in cancer and aging...
  47. pmc EGFRvIII expression and PTEN loss synergistically induce chromosomal instability and glial tumors
    Li Li
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Neuro Oncol 11:9-21. 2009
    ..These results provide a molecular basis for the occurrence of these two genetic lesions in brain tumors and point to a role in induction of genomic instability...
  48. ncbi On the road to cancer: aneuploidy and the mitotic checkpoint
    Geert J P L Kops
    Laboratory of Experimental Oncology, Department of Medical Oncology, University Medical Center, Utrecht, 3584 CG, The Netherlands
    Nat Rev Cancer 5:773-85. 2005
    ..Defects in the mitotic checkpoint generate aneuploidy and might facilitate tumorigenesis, but more severe disabling of checkpoint signalling is a possible anticancer strategy...
  49. ncbi Three classes of genes mutated in colorectal cancers with chromosomal instability
    Zhenghe Wang
    Sidney Kimmel Comprehensive Cancer Center and Howard Hughes Medical Institute at Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Cancer Res 64:2998-3001. 2004
    ..To determine whether genes shown to cause chromosomal instability in model systems were mutated in colorectal cancers, we identified their human homologues and determined ..
  50. ncbi Inactivation of Dnmt3b in mouse embryonic fibroblasts results in DNA hypomethylation, chromosomal instability, and spontaneous immortalization
    Jonathan E Dodge
    Cardiovascular Research Center and Cancer Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 280:17986-91. 2005
    ..These results suggest that DNA hypomethylation may induce genomic instability, which in turn leads to spontaneous immortalization or premature senescence of Dnmt3b-deficient MEFs via a p53-independent mechanism...
  51. ncbi CDC4 mutations occur in a subset of colorectal cancers but are not predicted to cause loss of function and are not associated with chromosomal instability
    Zoe Kemp
    Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK
    Cancer Res 65:11361-6. 2005
    ..Knockout of CDC4 in vitro in colorectal cancer cells causes changes suggestive of chromosomal instability (CIN)...
  52. ncbi Colonic polyposis caused by mTOR-mediated chromosomal instability in Apc+/Delta716 Cdx2+/- compound mutant mice
    Koji Aoki
    Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501, Japan
    Nat Genet 35:323-30. 2003
    ..High ABI in all cell lines was suppressed by mTOR inhibitors LY294002 and rapamycin. These results suggest that reduced expression of CDX2 is important in colon tumorigenesis through mTOR-mediated chromosomal instability.
  53. pmc Aurora-A expression is independently associated with chromosomal instability in colorectal cancer
    Yoshifumi Baba
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Neoplasia 11:418-25. 2009
    ..AURKA overexpression is observed in various cancers including colon cancer, and a link between AURKA and chromosomal instability (CIN) has been proposed...
  54. ncbi Can chromosomal instability initiate tumorigenesis?
    Franziska Michor
    Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Department of Mathematics, Harvard University, Cambridge, MA 02138, USA
    Semin Cancer Biol 15:43-9. 2005
    ..Mutations in those genes increase the net reproductive rate of cells. Chromosomal instability (CIN) is a feature of most human cancers...
  55. pmc Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability
    Muhan Chen
    Department of Clinical Oncology, Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China
    BMC Cancer 11:199. 2011
    ..In the present study, we aim to investigate the physiological and pathological effect of eIF-5A2 in an eIF-5A2 transgenic mouse model...
  56. pmc Deficiency in mammalian histone H2B ubiquitin ligase Bre1 (Rnf20/Rnf40) leads to replication stress and chromosomal instability
    Sophia B Chernikova
    Department of Radiation Oncology, Stanford University, Stanford, California 94305, USA
    Cancer Res 72:2111-9. 2012
    ....
  57. pmc Chromosomal instability and cancer: a complex relationship with therapeutic potential
    Samuel F Bakhoum
    Department of Biochemistry and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Clin Invest 122:1138-43. 2012
    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...
  58. pmc RAD51 mutants cause replication defects and chromosomal instability
    Tae Moon Kim
    Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas, USA
    Mol Cell Biol 32:3663-80. 2012
    ..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...
  59. pmc Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia through chromosomal instability and DNA hypermethylation
    Anjali Mishra
    Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA
    Cancer Cell 22:645-55. 2012
    ..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...
  60. pmc Specific synthetic lethal killing of RAD54B-deficient human colorectal cancer cells by FEN1 silencing
    Kirk J McManus
    Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC, Canada, V6T 1Z4
    Proc Natl Acad Sci U S A 106:3276-81. 2009
    ....
  61. ncbi Chromosomal instability, aneuploidy and routine high-resolution DNA content analysis in oral cancer risk evaluation
    Walter Giaretti
    Department of Diagnostic Oncology, Biophysics and Cytometry Section, IRCCS A O U San Martino IST, Largo Rosanna Benzi n 10, 16132, Genoa, Italy
    Future Oncol 8:1257-71. 2012
    ..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...
  62. pmc 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
    Kerstin Heselmeyer-Haddad
    Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Am J Pathol 181:1807-22. 2012
    ..The DCIS had a lower degree of chromosomal instability than the IDC...
  63. pmc An autosomal locus that controls chromosome-wide replication timing and mono-allelic expression
    Eric P Stoffregen
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 S W Sam Jackson Park Road, Portland, OR 97239, USA
    Hum Mol Genet 20:2366-78. 2011
    ..Taken together, these observations indicate that human autosomes contain discrete cis-acting loci that control chromosome-wide replication timing, mono-allelic expression and the stability of entire chromosomes...
  64. ncbi Linear model of colon cancer initiation
    Franziska Michor
    Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, USA
    Cell Cycle 3:358-62. 2004
    ..The majority of colorectal cancers present chromosomal instability, CIN, which is caused by mutations in genes that are required to maintain chromosomal stability...
  65. pmc Checkpoint-apoptosis uncoupling in human and mouse embryonic stem cells: a source of karyotpic instability
    Charlie Mantel
    Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine, and the Walther Cancer Institute, Indianapolis, IN 46202, USA
    Blood 109:4518-27. 2007
    ..Events causing chromosomal abnormalities in ESCs may be related to events in tumor cells causing chromosomal instability (CIN) in human disease. However, the underlying mechanisms are unknown...
  66. pmc Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability
    E Seemanova
    Department of Clinical Genetics, Institute of Biology and Medical Genetics, 2nd Medical School of Charles University, Prague, Czech Republic
    J Med Genet 43:218-24. 2006
    Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability disorder with hypersensitivity to ionising radiation...
  67. ncbi Resolution of anaphase bridges in cancer cells
    Diane R Hoffelder
    Department of Biological Sciences, University of Pittsburgh, 258 Crawford Hall, 15260, Pittsburgh, PA 15260, USA
    Chromosoma 112:389-97. 2004
    b>Chromosomal instability is a key step in the generation of the cancer cell karyotype. An indicator of unstable chromosomes is the presence of chromatin bridges during anaphase...
  68. ncbi Acquisition of high-level chromosomal instability is associated with integration of human papillomavirus type 16 in cervical keratinocytes
    Mark R Pett
    Medical Research Council Cancer Cell Unit, MRC Hutchison Research Centre, University of Cambridge, Hills Road, Cambridge CB2 2XZ, United Kingdom
    Cancer Res 64:1359-68. 2004
    ..b>Chromosomal instability is induced when HR-HPV E7 oncoprotein is overexpressed from heterologous promoters in vitro...
  69. pmc Activated oncogenes promote and cooperate with chromosomal instability for neoplastic transformation
    Richard A Woo
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong
    Genes Dev 18:1317-30. 2004
    Most cancer cells are aneuploid. The chromosomal instability hypothesis contends that aneuploidy is the catalyst for transformation, whereas the gene mutation hypothesis asserts that cancer is driven by mutations to proto-oncogenes and ..
  70. ncbi Mitotic chromosomal instability and cancer: mouse modelling of the human disease
    Juan Manuel Schvartzman
    Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nat Rev Cancer 10:102-15. 2010
    ..Mitotic chromosomal instability - the inability to faithfully segregate equal chromosome complements to two daughter cells during mitosis ..
  71. pmc Epigenetic instability and chromosomal instability in hepatocellular carcinoma
    Hiroto Katoh
    Pathology Division, National Cancer Center Research Institute, 5 1 1, Tsukiji, Chuo Ku, Tokyo 104 0045, Japan
    Am J Pathol 168:1375-84. 2006
    The aim of this study was to clarify the association between the epigenetic instability phenotype and the chromosomal instability phenotype in primary hepatocellular carcinoma (HCC). Sixty primary HCC tumors were examined...
  72. ncbi A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends
    Nancy S Bae
    Stowers Institute for Medical Research, Kansas City, MO 64110, USA
    Mol Cell 26:323-34. 2007
    ..Biochemical fractionation and reconstitution revealed that telomere protection is mediated by a RAP1/TRF2 complex, providing evidence for a direct role for human RAP1 in the protection of telomeric DNA from NHEJ...
  73. ncbi Genetic instability and the quasispecies model
    Yisroel Brumer
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
    J Theor Biol 241:216-22. 2006
    ..Microsatellite instability (MIN) leads to by elevated point mutation rates, whereas chromosomal instability (CIN) refers to increased rates of losing or gaining whole chromosomes or parts of chromosomes during ..
  74. pmc Genetic instability and clonal expansion
    Martin A Nowak
    Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
    J Theor Biol 241:26-32. 2006
    ....
  75. ncbi Targeting chromosomal instability and tumour heterogeneity in HER2-positive breast cancer
    REBECCA A BURRELL
    Translational Cancer Therapeutics Laboratory, London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    J Cell Biochem 111:782-90. 2010
    b>Chromosomal instability (CIN) is a common cause of tumour heterogeneity and poor prognosis in solid tumours and describes cell-cell variation in chromosome structure or number across a tumour population...
  76. ncbi LOH and copy neutral LOH (cnLOH) act as alternative mechanism in sporadic colorectal cancers with chromosomal and microsatellite instability
    Ralph Melcher
    Department of Medicine II, Division of Gastroenterology, University of Wurzburg, Oberdurrbacher Strasse 6, 97080 Wurzburg, Germany
    Carcinogenesis 32:636-42. 2011
    ..The aim of our study was to analyse tissue from MSI and MSS CRC for the existence of (frequently) deleted chromosomal regions and tumor suppressor genes located therein...
  77. pmc Haploinsufficiency of SGO1 results in deregulated centrosome dynamics, enhanced chromosomal instability and colon tumorigenesis
    Hiroshi Y Yamada
    Center for Chemoprevention and Cancer Drug Development, Department of Medicine, Medical Oncology Section, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
    Cell Cycle 11:479-88. 2012
    ..Together, these results suggest that haploinsufficiency of SGO1 causes enhanced CIN, colonic preneoplastic lesions and tumorigenesis in mice. SGO1 is essential for the suppression of CIN and tumor formation...
  78. pmc Deletion of p53 in human mammary epithelial cells causes chromosomal instability and altered therapeutic response
    M B Weiss
    University of Maryland Greenebaum Cancer Center, Baltimore, MD, USA
    Oncogene 29:4715-24. 2010
    ..Interestingly, p53 loss induced chromosomal instability leading to features of transformation and the selection of clones with varying phenotypes...
  79. ncbi Genomic signatures of chromosomal instability and osteosarcoma progression detected by high resolution array CGH and interphase FISH
    S Selvarajah
    Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
    Cytogenet Genome Res 122:5-15. 2008
    ..There have been no analyses to date documenting genomic signatures consistent with chromosomal instability mechanisms in OS tumors using array CGH...
  80. pmc Prostate-specific membrane antigen associates with anaphase-promoting complex and induces chromosomal instability
    Sigrid A Rajasekaran
    Nemours Center for Childhood Cancer Research, Alfred I duPont Hospital for Children, Rockland Center I, 1701 Rockland Road, Wilmington, DE 19803, USA
    Mol Cancer Ther 7:2142-51. 2008
    ..Thus, these findings provide the first evidence that PSMA has a causal role in the induction of aneuploidy and might play an etiologic role in the progression of prostate cancer...
  81. ncbi Telomere dysfunction and chromosome structure modulate the contribution of individual chromosomes in abnormal nuclear morphologies
    J Pampalona
    Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra, Spain
    Mutat Res 683:16-22. 2010
    ..of end-to-end chromosome fusions that can enter into breakage-fusion-bridge cycles generating massive chromosomal instability. In human mammary epithelial cells, different types of abnormal nuclear morphologies were observed, ..
  82. ncbi Numerical and structural centrosome aberrations are an early and stable event in the adenoma-carcinoma sequence of colorectal carcinomas
    Gian Kayser
    Institute of Pathology, University Hospital Freiburg, Germany
    Virchows Arch 447:61-5. 2005
    ..Here, we specifically address centrosome aberrations in the adenoma-carcinoma sequence of colorectal cancer by detailed evaluation of gamma-tubulin staining patterns...
  83. pmc Chromatin dynamics during repair of chromosomal DNA double-strand breaks
    Manisha Sinha
    Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA
    Epigenomics 1:371-85. 2009
    ..Even a single, unrepaired DSB can be a lethal event, or such unrepaired damage can result in chromosomal instability and loss of genetic information...
  84. ncbi Chromosomal instability: a composite phenotype that influences sensitivity to chemotherapy
    Sarah E McClelland
    Translational Cancer Therapeutics Laboratory, Cancer Research UK, London Research Institute, London, UK
    Cell Cycle 8:3262-6. 2009
    b>Chromosomal instability (CIN) is defined as continual gain or loss of whole chromosomes or fractions of chromosomes and is a major cause of the genomic instability that characterizes most solid tumors...
  85. ncbi Alternative lengthening of telomeres--an enhanced chromosomal instability in aggressive non-MYCN amplified and telomere elongated neuroblastomas
    Gisela Lundberg
    Department of Clinical Genetics, Lund University, University and Regional Laboratories, Skane University Hospital, Lund, Sweden
    Genes Chromosomes Cancer 50:250-62. 2011
    ..In the present study, telomere-dependent chromosomal instability and telomere length were determined in six NB cell lines and fifty tumor biopsies...
  86. pmc Knockdown of mu-calpain in Fanconi anemia, FA-A, cells by siRNA restores alphaII spectrin levels and corrects chromosomal instability and defective DNA interstrand cross-link repair
    Pan Zhang
    Department of Pathology and Laboratory Medicine, New Jersey Medical School and Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA
    Biochemistry 49:5570-81. 2010
    ..stability of alphaIISp and correlates with a decreased level of repair of DNA interstrand cross-links and chromosomal instability in FA cells...
  87. pmc Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype
    Laura Lentini
    Department of Cellular and Developmental Biology A, Monroy, University of Palermo, Viale delle Scienze, Palermo, Italy
    BMC Cancer 7:212. 2007
    ..Also, alterations in genes required for mitotic progression could be involved in CIN.A major candidate is represented by Aurora-A/STK15 that associates with centrosomes and is overexpressed in several types of human tumour...
  88. ncbi Essential role for nuclear PTEN in maintaining chromosomal integrity
    Wen Hong Shen
    Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
    Cell 128:157-70. 2007
    ..We propose that PTEN acts as a guardian of genome integrity...
  89. ncbi Integrative approach for prioritizing cancer genes in sporadic colon cancer
    James F Reid
    Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Italy
    Genes Chromosomes Cancer 48:953-62. 2009
    ....
  90. ncbi Patterns of genomic instability in gastric cancer: clinical implications and perspectives
    L Ottini
    Department of Experimental Medicine and Pathology, University La Sapienza, Rome
    Ann Oncol 17:vii97-102. 2006
    ..This review describes our current knowledge of the instability pathways in gastric carcinogenesis and the potential clinical applications for different forms of genomic instability in GC...
  91. ncbi Genomic mechanisms and measurement of structural and numerical instability in cancer cells
    Jane Bayani
    Division of Applied Molecular Oncology, Princess Margaret Hospital, University Health Network, 610 University Avenue, Room 9 717, Toronto, Ontario, Canada M5G 2M9
    Semin Cancer Biol 17:5-18. 2007
    ..b>Chromosomal instability (CIN) describes the excessive rate of numerical and structural genomic change in tumors...
  92. pmc The requirement of p53 for maintaining chromosomal stability during tetraploidization
    Chui Chui Ho
    Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong
    Oncotarget 1:583-95. 2010
    ..In contrast, impairment of p53 functions after tetraploids were established was ineffective in triggering chromosomal instability and transformation...
  93. pmc Telomere loss as a mechanism for chromosome instability in human cancer
    John P Murnane
    Department of Radiation Oncology, University of California San Francisco, San Francisco, CA 94143 1331, USA
    Cancer Res 70:4255-9. 2010
    ..Cancer Res; 70(11); 4255-9. (c)2010 AACR...
  94. ncbi Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs
    Karen E Gascoigne
    Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
    Cancer Cell 14:111-22. 2008
    ..We present data supporting a model wherein cell fate is dictated by two competing networks, one involving caspase activation, the other protecting cyclin B1 from degradation...
  95. ncbi VHL loss causes spindle misorientation and chromosome instability
    Claudio R Thoma
    Institute of Cell Biology, ETH Zurich, 8093 Zurich, Switzerland
    Nat Cell Biol 11:994-1001. 2009
    ..cells and its functional inactivation provokes spindle misorientation, spindle checkpoint weakening and chromosomal instability. Spindle misorientation is linked to unstable astral microtubules and is supressed by the restoration of ..
  96. ncbi Breast cancer survival is associated with telomere length in peripheral blood cells
    Ulrika Svenson
    Department of Medical Biosciences Pathology, Umea University, Umea, Sweden
    Cancer Res 68:3618-23. 2008
    ..92; 95% CI, 1.33-6.39; P = 0.007). Our results indicate that blood RTL may serve as a prognostic indicator in breast cancer patients with advanced disease...
  97. pmc Instability of pathogenicity islands in uropathogenic Escherichia coli 536
    Barbara Middendorf
    Institut für Molekulare Infektionsbiologie, Universitat Wurzburg, 97070 Wurzburg, Germany
    J Bacteriol 186:3086-96. 2004
    ..Such extrachromosomal derivatives of PAI II536 and PAI III536 were detected by a specific PCR assay. Our data indicate that the genome content of uropathogenic E. coli can be modulated by deletion of PAIs...
  98. ncbi Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy
    Takeshi Tomonaga
    Department of Molecular Diagnosis F8, Graduate School of Medicine, Chiba University, Inohana, Chuo Ku, Chiba, Japan
    Cancer Res 65:4683-9. 2005
    b>Chromosomal instability (CIN) has been recognized as a hallmark of human cancer and is caused by continuous chromosome missegregation during mitosis...
  99. ncbi Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex changes and multiple forms of chromosomal instability in colorectal cancers
    Michelle Gaasenbeek
    Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, UK
    Cancer Res 66:3471-9. 2006
    Cancers with chromosomal instability (CIN) are held to be aneuploid/polyploid with multiple large-scale gains/deletions, but the processes underlying CIN are unclear and different types of CIN might exist...
  100. ncbi Centrosome overduplication, chromosomal instability, and human papillomavirus oncoproteins
    Anette Duensing
    Molecular Virology Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA 15213, USA
    Environ Mol Mutagen 50:741-7. 2009
    ..These findings underscore that the HPV-16 E7 oncoprotein is a unique tool to dissect normal and abnormal centriole biogenesis and the underlying molecular circuitry...
  101. doi Deregulation of the centrosome cycle and the origin of chromosomal instability in cancer
    Wilma L Lingle
    Mayo Clinic College of Medicine, Mayo Clinic Foundation, Mayo Clinic Cancer Center, Rochester, Minnesota 55905, USA
    Adv Exp Med Biol 570:393-421. 2005
    ..cause chromosome missegregation in sea urchin eggs, there is still much left to discover with regard to chromosomal instability in cancer...

Research Grants72

  1. Optimization of DNA Repair by Abh8
    Lauren Endres; Fiscal Year: 2013
    ..Overall, these findings will form the basis of future studies into Abh8 regulation during the DDR. ..
  2. Enterococcus faecalis, Colorectal Cancer, and Bystander Effects
    Mark M Huycke; Fiscal Year: 2012
    ..the oxidative physiology of this common intestinal commensal, Enterococcus faecalis, to the origin of chromosomal instability (CIN). Among intestinal commensals E...
  3. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2013
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
  4. Folate Status, Genomic Uracil, and the Balance of Base Excision Repair Activity
    Michael D Wyatt; Fiscal Year: 2011
    ..hypothesis to be tested is that BER initiated by uracil DNA glycosylases during folate depletion causes chromosomal instability, which is procarcinogenic to normal epithelial cells and anticarcinogenic to established adenocarcinoma ..
  5. Interrelationships among nutrients involved in one-carbon metabolism in Banglades
    MEGAN NINA HALL; Fiscal Year: 2011
    ....
  6. Herpesvirus-induced telomerase dysregulation and tumor formation
    Keith William Jarosinski; Fiscal Year: 2011
    ..It will also address the mechanism of herpesvirus integration into the host genome and its importance for latent infection and transformation of lymphocytes. ..
  7. MECHANISMS OF INTESTINAL TUMORIGENESIS
    Vincent W Yang; Fiscal Year: 2013
    ..the manifestation of genetic instability that is present in CRC, of which there are two distinct forms: chromosomal instability (CIN) and microsatellite instability (MIN)...
  8. Development of a Porcine Model of Ataxia-Telangiectasia
    Christopher Rogers; Fiscal Year: 2011
    ..to cancer (lymphomas, leukemia, brain tumors), immunodeficiency, insulin-resistant diabetes, chromosomal instability, sensitivity to ionizing radiation, susceptibility to bronchopulmonary disease, and the nearly complete ..
  9. Roles of the mammalian CST complex in DNA replication and chromosome cohesion
    JASON AARON STEWART; Fiscal Year: 2013
    ..The completion of these studies will advance our understanding of these cellular processes and provide new targets for prevention and treatment of these diseases. ..
  10. Mechanisms of arsenic-induced chromosomal instability and carcinogenesis
    Wei Dai; Fiscal Year: 2013
    ..We have recently shown that As(III) induces chromosomal instability by suppressing the activation of BubR1, a cell cycle checkpoint protein, leading to unscheduled ..
  11. Development of a Porcine Model of Ataxia-Telangiectasia
    Christopher Rogers; Fiscal Year: 2013
    ..to cancer (lymphomas, leukemia, brain tumors), immunodeficiency, insulin-resistant diabetes, chromosomal instability, sensitivity to ionizing radiation, susceptibility to bronchopulmonary disease, and the absence, or ..
  12. Centromere Structure and Function in Candida albicans
    Judith G Berman; Fiscal Year: 2012
    ..We will develop tools to study this process and will identify companion drugs that inhibit these defects, thereby extending the usefulness of available antifungal therapies. ..
  13. ANALYSIS OF NEMATODE SEX DETERMINATION
    Barbara J Meyer; Fiscal Year: 2013
    ..Our protein complexes give us insight into the mechanisms underlying the genome rearrangements associated with such a cancerous state. ..
  14. FASEB SRC on Yeast Chromosome Structure, Replication and Segregation
    Scott Keeney; Fiscal Year: 2012
    ..This conference brings together the principal investigators studying chromosome biology in yeasts. ..
  15. C MYC--TRANSCRIPTION AND APOPTOSIS
    Chi V Dang; Fiscal Year: 2011
    ..Our data not only indicate that tumorigenesis of the Myc-dependent P493 cells is not associated with chromosomal instability, but they also indicate that anti-oxidants inhibit tumorigenesis through enhancing the degradation of HIF-..
  16. Recombination Repair Complex in Human Cells
    Richard Fishel; Fiscal Year: 2013
    ..b>Chromosomal instability resulting from recombination repair (RR) defects have been linked to a variety of human cancers including ..
  17. Establishment of sister chromatid cohesion
    Douglas E Koshland; Fiscal Year: 2013
    ..Mutations in human genes encoding Smc proteins have been linked to cancer, birth defects and disorders. ..
  18. Plk1-Numb Cooperation in Melanomagenesis
    Nihal Ahmad; Fiscal Year: 2013
    ..Plk1 dysregulation has been shown to result in chromosomal instability, aneuploidy and tumor development...
  19. Regulation and Function of hTERT in Human Cells
    William C Hahn; Fiscal Year: 2013
    ..In addition, these studies will provide a foundation for strategies to manipulate these complexes therapeutically. ..
  20. Nutrients involved 1-carbon metabolism and the methylation of arsenic and DNA
    MEGAN NINA HALL; Fiscal Year: 2013
    ..Hall will have developed into an independent multidisciplinary investigator well positioned to develop additional hypotheses related to the role of nutrient/environment interactions in disease development. ..
  21. Genetic Analysis of MSM Protein Function in S. Pombe
    Susan L Forsburg; Fiscal Year: 2012
    ..This project uses genetics and cell biology in a simple yeast to study how these conserved proteins normally work to protect the genome, and to study the molecular consequences when they are disrupted. ..
  22. Telomeres and lung cancer incidence and survival
    Jennifer Anne Doherty; Fiscal Year: 2013
    ..Alternatively, critically short telomeres can cause chromosomal instability and fusions, allowing the accumulation of genetic changes in favor of carcinogenesis...
  23. Genetic Analysis of Ataxia-telangiectasia
    DAVID WASSARMAN; Fiscal Year: 2012
    ..Cells derived from A-T patients exhibit chromosomal instability and hypersensitivity to DNA damaging agents...
  24. Telomere dysfunction, chromosome 9 instability and bladder cancer risk
    Yun Ling Zheng; Fiscal Year: 2013
    ..In contrast, genetic factors that contribute to the risk of TCC are less well understood. Chromosomal instability (CIN) is the dominant form of the genomic alterations seen in bladder tumors and telomere dysfunction may ..
  25. Molecular Mechanisms of Histone Acetyltransferases
    John M Denu; Fiscal Year: 2012
    ..To elucidate the 'histone code'read by modular chromatin-binding domains. 3.) To determine the function of chromatin-binding modules in substrate selection and catalytic efficiency by chromatin PTM complexes. ..
  26. Mechanisms of PASG-Mediated Senescence in Hematopoietic Development and Leukemia
    ROBERT JOHN ARCECI; Fiscal Year: 2010
    ..These studies should provide significant information concerning mechanisms of epigenetic patterning and gene expression in normal hematopoiesis and leukemia as well as in risk-group and epigenetically-directed therapies. ..
  27. The interaction of Chlamydia with the host cytoskeleton
    Scott S Grieshaber; Fiscal Year: 2012
    ..Determining the mechanisms of chlamydial intracellular development and its impact on host cell replication machinery will lead to advances in understanding chlamydial disease and offer potential novel therapeutic targets. ..
  28. Regulation and Dysregulation of Antibody Diversification
    MATTHEW STROUT; Fiscal Year: 2013
    ..This research will serve to identify how genes are normally protected from this activity and will define how a breakdown of protective mechanisms leads to the development of hematologic cancers...
  29. Epigenetic Regulation of Medulloblastoma
    LAURIE L JACKSON-GRUSBY; Fiscal Year: 2012
    ..tumor context, Dnmt1 hypomorphic mice have revealed important roles for DNA hypomethylation in promoting chromosomal instability and alternatively in preventing aberrant gene silencing...
  30. Small RNA and whole chromosome recognition in Drosophila melanogaster.
    Victoria H Meller; Fiscal Year: 2013
    ..The similarities between analogous processes in flies and mammals suggest that this mechanism may also contribute to normal genome regulation in humans. ..
  31. Characterization of JNK in Cell Cycle Control
    ZE apos EV A RONAI; Fiscal Year: 2012
    ..Using biochemical, cellular and genetic models our proposed studies will delineate the requirements and regulation of this newly identified regulatory lobe along the cell cycle and DNA damage response. ..
  32. PTEN Deficiency and Tumor Development
    Yuxin Yin; Fiscal Year: 2012
    ..Identification of the PTEN-mitotic pathway may offer a profound implication for development of therapeutic strategies against tumorigenesis. ..
  33. Stress, Mood, Omega-3 Fatty Acids, &Telomeric Aging: Randomized Controlled Trial
    Janice K Kiecolt-Glaser; Fiscal Year: 2012
    ..By adding cell aging assessments to an ongoing randomized controlled trial of omega-3 supplementation, we can assess how omega-3 supplementation affects both telomerase activity and telomere length, as well as possible mechanisms. ..
  34. ROCK II-mediated regulation of centrosome duplication / centrosome amplification
    Kenji Fukasawa; Fiscal Year: 2013
    ....
  35. PyroMark Q96 MD
    Marisa S Bartolomei; Fiscal Year: 2010
    ..The technology afforded by the PyroMark Q96 MD will allow a more complete, accurate and efficient understanding of the role of DNA methylation changes in development, behavior, environmental exposures and disease. ..
  36. Radiation and Genomic Instability in Finite Lifespan Human Mammary Epithelium
    Amy Kronenberg; Fiscal Year: 2010
    ..We will test the central hypothesis that exposure to ionizing radiation (x-rays) will elicit chromosomal instability in the clonal descendants of finite lifespan human mammary epithelial cells (HMEC)...
  37. Genome-wide analysis identifies genes required for repair of DNA strand breaks
    LYSLE KEVIN LEWIS; Fiscal Year: 2012
    ..The proposed work will investigate the functions of over 40 yeast genes recently shown to protect DNA integrity. Most of the protective yeast genes share strong sequence similarity with human genes which may serve similar functions. ..
  38. Molecular mechanisms underlying chromosomal instability and aneuploidy
    Wei Dai; Fiscal Year: 2012
    ....
  39. Nucleoporins in Chromosomal Instability and Cancer
    Jan M van Deursen; Fiscal Year: 2012
    ..into the biological relevance of these nuclear transport factors and their possible role in preventing chromosomal instability and tumorigenesis...
  40. Functions of Histone Ubiquitination and Methylation
    Zu Wen Sun; Fiscal Year: 2010
    ..Aim 2. Define the roles of phosphorylation and acetylation on Rad6. Aim 3. Determine the molecular mechanisms of action of Rad6-mediated H2B ubiquitination in establishing histone H3 methylation. ..
  41. DISSECTION OF THE DNA DAMAGE CHECKPOINT PATHWAYS
    Yolanda Sanchez; Fiscal Year: 2009
    ..In aim III we will address the physiological significance of both the interaction of Chk1 with centrosomal proteins and the localization of Chk1 to centrosomes. ..
  42. The Novel Role of Branch Migration Protein Rad54 in Maintaining Genome Stability
    MATTHEW JOHN ROSSI; Fiscal Year: 2011
    ..Double RAD54 BLM knockouts show a dramatic increase in chromosomal instability over the level observed in either single knockout, indicating a functional redundancy between these two ..
  43. Analysis of Human Telomeric Structural Variation
    Harold C Riethman; Fiscal Year: 2010
    ....
  44. MicroRNAs and chromosome 22q in the colon
    Anil K Rustgi; Fiscal Year: 2012
    ..It is well accepted that the majority of sporadic colorectal cancers feature the chromosomal instability pathway, involving alterations in key tumor suppressor genes (APC and p53, but also SMAD4) and oncogenes (..
  45. TRANSPOSASE PROTEIN METNASE IN LEUKEMIC DECATENATION
    Robert A Hromas; Fiscal Year: 2011
    ..Preventing such chromosome breakage can reduce the mutations that cause many forms of cancer. The cancer cell, however, can subvert Metnase, and use it to resist the actions of DNA damaging chemotherapy. ..
  46. Protection of Centromeric Cohesion by Bub1 and Sgo1
    Hongtao Yu; Fiscal Year: 2010
    ..research will shed light on the mechanism of chromosome segregation and may in turn lead to better understanding and prevention of chromosomal instability and aneuploidy in human cancers and birth defects, such as Down Syndrome.
  47. RNAi-Mediated Heterochromatin Assembly
    Danesh Moazed; Fiscal Year: 2013
    ..The ultimate goal of these studies is a complete molecular understanding of gene silencing. ..
  48. JC Virus and Human Colorectal Neoplasia
    CLEMENT R BOLAND; Fiscal Year: 2013
    ..Importantly, we can induce chromosomal instability (CIN) in several in vitro colonic epithelial cell modes, which permit us to study these transformation-..
  49. Aurora-A/BTAK/STK15 Oncoprotein in Mitotic Spindle Assembly and Checkpoint Respon
    Subrata Sen; Fiscal Year: 2012
    ..is a critical regulator of mitotic chromosome segregation and a putative oncoprotein capable of inducing chromosomal instability and oncogenic transformation when ectopically over expressed in mammalian cells in vitro and in vivo...
  50. Role of Parkinson's disease gene PARK2 in GBM oncogenesis and genomic instability
    TIMOTHY AN THY CHAN; Fiscal Year: 2013
    ..abstract_text> ..
  51. Structure and Function of Human Telomerase
    JULI F FEIGON; Fiscal Year: 2013
    ..The results of these investigations will provide a molecular basis for understanding telomerase activity as well as how mutations linked to disease affect activity, and for designing drugs that target TR. ..
  52. Structural mechanisms of Mcm10 in DNA replication
    Brandt F Eichman; Fiscal Year: 2010
    ..A higher resolution description of key replication factors and their intermolecular interactions will lay the foundation for the possible development of therapeutic agents against cancer and other human disease. ..
  53. Roles of the Fanconi Anemia Pathway in Bladder Tumorigenesis
    Peiwen Fei; Fiscal Year: 2013
    ..Importantly, overexpression of FAVL can impair the FA pathway, promote chromosomal instability, and confer cell growth advantages in vitro and in vivo...
  54. Technology for detection and quantitation of telomeric DNA aberrations in cancer
    Harold C Riethman; Fiscal Year: 2012
    ....
  55. High Throughput Screens of Novel Radiation Sensitizers and Protectors
    William F Morgan; Fiscal Year: 2011
    ..sensitizer or protector are not more likely to manifest genomic instability as measured by delayed chromosomal instability. All technology and cell lines are available and in place at the University of Maryland...
  56. Centrosome Mis-Regulation and Blood Vessel Function
    Victoria L Bautch; Fiscal Year: 2013
    ....
  57. CELL CYCLE CHECKPOINT CONTROL IN RESPONSE TO DNA DAMAGE
    Nancy C Walworth; Fiscal Year: 2011
    ..Our studies make use of the excellent genetics of this organism to elucidate mechanisms that are universally important for governing cell division in the face of DNA damage. ..
  58. MECHANISM OF ACTION OF YEAST SILENCING COMPLEXES
    Danesh Moazed; Fiscal Year: 2013
    ....
  59. Polyploidy, aneuploidy and genome stability
    DAVID S PELLMAN; Fiscal Year: 2013
    ..grant that defined 'ploidy-specific lethality', where genes that are not essential in normal diploid cells become essential in polyploid cells or extra centrosome-containing cells that have a chromosomal instability phenotype.
  60. Particulate Cr(VI) Toxicology in Human Lung Epithelial Cells and Fibroblasts
    John Pierce Wise; Fiscal Year: 2013
    ..Finally, we will have established a mechanistic model in a human lung cell system that will allow us to conduct studies for other factors important for preventing human lung cancer both generally and by other agents. ..
  61. FORMATION, STRUCTURE AND FUNCTION IN HETEROCHROMATIN
    Sarah C R Elgin; Fiscal Year: 2011
    ..Taken together these studies will illuminate how heterochromatin formation is initiated and sustained, and will provide new insights into gene regulation at the domain level. ..
  62. Interaction Between SV40 Large T and p185 Cullin
    James A DeCaprio; Fiscal Year: 2011
    ..In addition, we will determine if T Ag's ability to induce chromosomal instability is dependent, at least in part, on perturbation of CUL7 and FBXW8 function...
  63. REGULATION OF P53 IN CERVICAL CARCINOMA BY HEAT/HYPOXIA
    Amato Giaccia; Fiscal Year: 1999
    ....
  64. 12th International Workshop on Ataxia-Telangiectasia and ATM
    Richard Gatti; Fiscal Year: 2006
    ..A-T is characterized by progressive cerebellar ataxia, telangiectasia, immunodeficiency, chromosomal instability, radiation sensitivity and increased incidence of lymphoid malignancies...
  65. FAA AND FAD GENES AND PROTEINS
    Manuel Buchwald; Fiscal Year: 1999
    ..The fifth aim is to isolate the FAE gene by the expression cloning used so successfully to date. ..
  66. Small-molecule inhibitors of the human RECQ1 and Bloom DNA helicases
    Opher Gileadi; Fiscal Year: 2009
    ..Shutting down the expression of RECQ1 or BLM leads to chromosomal instability and higher radiation sensitivity in cultured cells...
  67. Cadmium Cytoskeletal Toxicology in the Lung
    Iih Nan Chou; Fiscal Year: 2005
    ..into functional deficiencies resulting in pathological consequences namely, cell cycle perturbation and chromosomal instability, two key events intrinsically involved in the mechanisms of Cd chemical pathology leading to lung ..
  68. Development of a HTS Assay Targeting End Protection of Telomeres
    DEBORAH WUTTKE; Fiscal Year: 2007
    ..Small molecules that specifically target telomeres will provide valuable tools for dissecting the mechanism of telomere function and lay the groundwork for the discovery of cancer therapeutics. [unreadable]..
  69. FoxM1B Protein in Stimulating Proliferation during Aging
    LESTER LAU; Fiscal Year: 2007
    ..abstract_text> ..
  70. GENOMIC STABILITY AND AGING IN YEAST
    Steven Brill; Fiscal Year: 2003
    Werner's Syndrome (WS) is a genetic disease characterized by premature aging and chromosomal instability. The gene responsible for WS (WRN) is similar to the SGS1 gene of yeast and, like WS, SGS1 mutants display premature aging and ..
  71. MUTAGEN SENSITIVITY & PROGRESSION IN BARRETTS ESOPHAGUS
    DIANA FARROW; Fiscal Year: 1999
    ..The overall goal of the proposed study is to determine whether chromosomal instability, as measured in vitro in cultured lymphocytes by the bleomycin sensitivity assay, or in vivo as allelic ..
  72. Analysis of Loss of Function of MAD2 in Mammals
    Loren Michel; Fiscal Year: 2006
    ..The effects on development, chromosome stability, and tumorigenesis of tissue specific Mad2 null mutations will be studied. ..