Mutation in the mismatch repair gene Msh6 causes cancer susceptibility

Cell. 1997 Nov 14;91(4):467-77. doi: 10.1016/s0092-8674(00)80433-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • Animals
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • Cytoskeletal Proteins / analysis
  • DNA Repair / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Gastrointestinal Neoplasms / chemistry
  • Gastrointestinal Neoplasms / genetics
  • Genes, APC
  • Genetic Predisposition to Disease
  • Germ-Line Mutation / physiology
  • Heterozygote
  • Homozygote
  • Lymphoma / genetics
  • Lymphoma / pathology
  • Male
  • Mice
  • Mice, Mutant Strains
  • Microsatellite Repeats / genetics
  • Molecular Sequence Data
  • Mutation / physiology*
  • Neoplasms / chemistry
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • RNA, Messenger / analysis


  • Adenomatous Polyposis Coli Protein
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • Msh6 protein, mouse
  • RNA, Messenger

Associated data

  • GENBANK/AF031085
  • GENBANK/AF031086
  • GENBANK/AF031087