Mutation in the mismatch repair gene Msh6 causes cancer susceptibility.

Journal Article (Journal Article)

Mice carrying a null mutation in the mismatch repair gene Msh6 were generated by gene targeting. Cells that were homozygous for the mutation did not produce any detectable MSH6 protein, and extracts prepared from these cells were defective for repair of single nucleotide mismatches. Repair of 1, 2, and 4 nucleotide insertion/deletion mismatches was unaffected. Mice that were homozygous for the mutation had a reduced life span. The mice developed a spectrum of tumors, the most predominant of which were gastrointestinal tumors and B- as well as T-cell lymphomas. The tumors did not show any microsatellite instability. We conclude that MSH6 mutations, like those in some other members of the family of mismatch repair genes, lead to cancer susceptibility, and germline mutations in this gene may be associated with a cancer predisposition syndrome that does not show microsatellite instability.

Full Text

Duke Authors

Cited Authors

  • Edelmann, W; Yang, K; Umar, A; Heyer, J; Lau, K; Fan, K; Liedtke, W; Cohen, PE; Kane, MF; Lipford, JR; Yu, N; Crouse, GF; Pollard, JW; Kunkel, T; Lipkin, M; Kolodner, R; Kucherlapati, R

Published Date

  • November 14, 1997

Published In

Volume / Issue

  • 91 / 4

Start / End Page

  • 467 - 477

PubMed ID

  • 9390556

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/s0092-8674(00)80433-x


  • eng

Conference Location

  • United States