Mutation in the mismatch repair gene Msh6 causes cancer susceptibility

Winfried Edelmann, Kan Yang, Asad Umar, Joerg Heyer, Kirkland Lau, Kunhua Fan, Wolfgang Liedtke, Paula E. Cohen, Michael F. Kane, James R. Lipford, Nianjun Yu, Gray F. Crouse, Jeffrey W. Pollard, Thomas Kunkel, Martin Lipkin, Richard Kolodner, Raju Kucherlapati

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292 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)467-477
Number of pages11
JournalCell
Volume91
Issue number4
DOIs
StatePublished - Nov 14 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Edelmann, W., Yang, K., Umar, A., Heyer, J., Lau, K., Fan, K., Liedtke, W., Cohen, P. E., Kane, M. F., Lipford, J. R., Yu, N., Crouse, G. F., Pollard, J. W., Kunkel, T., Lipkin, M., Kolodner, R., & Kucherlapati, R. (1997). Mutation in the mismatch repair gene Msh6 causes cancer susceptibility. Cell, 91(4), 467-477. https://doi.org/10.1016/S0092-8674(00)80433-X