Roles of the DNA mismatch repair genes in colorectal tumorigenesis

International Journal of Cancer. Journal International Du Cancer
C R Boland

Abstract

A rapid increase in our understanding of the basic mechanisms involved in the genesis of colorectal cancer has occurred. Important factors include the activation of oncogenes, the inactivation of tumor suppressor genes and the inactivation of DNA repair systems. Hereditary non-polyposis colorectal cancer (HNPCC) has been linked to germ-line mutations that inactivate one allele of a DNA mismatch repair gene, which pre-disposes affected individuals to a high frequency of early-onset cancer. We have developed a cellular model to study HNPCC using the DNA mismatch repair-deficient colon cancer cell line HCT116 and corrected the genetic deficiency by chromosome transfer. Human chromosome 3 corrected all manifestations of DNA mismatch repair deficiency in the cell line and restored sensitivity to the toxic effects of certain DNA alkylating agents. Data suggest that the DNA mismatch repair genes not only participate in the recognition and repair of DNA mismatches during new strand synthesis but may also signal cell cycle arrest in the face of overwhelming DNA damage. Additional functions for the DNA mismatch repair genes in the maintenance of DNA replicative fidelity are being studied.

References

Jan 25, 1991·Cell·J M Bishop
Apr 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·A G Knudson
Aug 2, 1995·Journal of the National Cancer Institute·G Marra, C R Boland
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A KatP Modrich
May 7, 1993·Science·L A AaltonenS R Hamilton
May 7, 1993·Science·S N ThibodeauD Schaid

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Citations

Feb 13, 2001·The American Journal of Pathology·J AlexanderS R Hamilton
Jul 21, 2004·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Henry T LynchJane F Lynch
Feb 28, 2003·Surgical Oncology Clinics of North America·Asif Rashid
Aug 16, 2001·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·N S Goldstein
Jun 9, 2001·Seminars in Surgical Oncology·E SeregniE Bombardieri
Oct 23, 1997·Diseases of the Colon and Rectum·S Baba
Sep 7, 2002·The British Journal of Nutrition·C I R Gill, I R Rowland
Jul 9, 2002·Journal of Cutaneous Pathology·Mahmoud R Hussein, Gary S Wood
May 20, 1998·Cancer·I I ArzimanoglouH R Barber
Feb 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sang-Heon LeeGary S Firestein
Dec 31, 1997·Hospital Practice·C R Boland
Jul 24, 1998·Mutation Research·K R TindallT A Kunkel

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