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
Language
- eng
Conference Location
- United States