Do MSH6 mutations contribute to double primary cancers of the colorectum and endometrium?

Hum Genet. 2000 Dec;107(6):623-9. doi: 10.1007/s004390000417.


Mismatch repair (MMR) gene mutations cause hereditary nonpolyposis colorectal cancer (HNPCC), a common form of familial colorectal cancer. Among MMR genes, germline MSH6 mutations are often observed in HNPCC-like families with an increased frequency of endometrial cancer. We have previously shown that a proportion of women affected with double primary cancers of the colorectum and endometrium carry germline MSH2 or MLH1 mutations and, thus, belong to HNPCC families. In this study, we have investigated the specific contribution of MSH6 defects to such double primary patients. By sequence analysis of the entire coding region of MSH6, three putative missense mutations were identified in patients with atypical family histories that do not meet HNPCC criteria. Moreover, one of these mutations, a novel substitution Arg901 His, was found in a patient previously shown to carry a truncating germline MLH1 mutation. Thus, MSH6 mutations are likely to contribute to the etiology of double primary cancers of the colorectum and endometrium.

Publication types

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

MeSH terms

  • Base Pair Mismatch
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Mutational Analysis
  • DNA Repair
  • DNA-Binding Proteins / genetics*
  • Endometrial Neoplasms / genetics*
  • Female
  • Germ-Line Mutation
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Neoplasms, Multiple Primary / genetics*
  • Pedigree


  • DNA-Binding Proteins
  • G-T mismatch-binding protein

Associated data

  • GENBANK/U54777
  • GENBANK/U73732
  • GENBANK/U73733
  • GENBANK/U73734
  • GENBANK/U73735
  • GENBANK/U73736
  • GENBANK/U73737