Mutation analysis of the CHK2 gene in families with hereditary breast cancer

Br J Cancer. 2001 Jul 20;85(2):209-12. doi: 10.1054/bjoc.2001.1858.

Abstract

Recently CHK2 was functionally linked to the p53 pathway, and mutations in these two genes seem to result in a similar Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL) multi-cancer phenotype frequently including breast cancer. As CHK2 has been found to bind and regulate BRCA1, the product of one of the 2 known major susceptibility genes to hereditary breast cancer, it also more directly makes CHK2 a suitable candidate gene for hereditary predisposition to breast cancer. Here we have screened 79 Finnish hereditary breast cancer families for germline CHK2 alterations. Twenty-one of these families also fulfilled the criteria for LFL or LFS. All families had previously been found negative for germline BRCA1, BRCA2 and TP53 mutations, together explaining about 23% of hereditary predisposition to breast cancer in our country. Only one missense-type mutation, Ile(157)-->Thr(157), was detected. The high Ile(157)--> Thr(157)mutation frequency (6.5%) observed in healthy controls and the lack of other mutations suggest that CHK2 does not contribute significantly to the hereditary breast cancer or LFL-associated breast cancer risk, at least not in the Finnish population. For Ile(157)--> Thr(157)our result deviates from what has been reported previously.

Publication types

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

MeSH terms

  • Breast Neoplasms / genetics*
  • Checkpoint Kinase 2
  • Cohort Studies
  • Female
  • Germ-Line Mutation*
  • Humans
  • Male
  • Pedigree
  • Protein Kinases / genetics*
  • Protein Serine-Threonine Kinases*

Substances

  • Protein Kinases
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein Serine-Threonine Kinases