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

Recently CHK2 was functionally linked to the p53 pathway, and mutations in these two genes seem to result in a similar L-Fraumeni syndrome (LFS) or Li -Fraumeni-like syndrome (LFL) multi-cancer phenotype frequently including b reast cancer. As CHK2 has been found to bind and regulate BRCA1, the produc t of one of the 2 known major susceptibility genes to hereditary breast can cer, it also more directly makes CHK2 a suitable candidate gene for heredit ary predisposition to breast cancer. Here we have screened 79 Finnish hered itary breast cancer families for germline CHK2 alterations. Twenty-one of t hese families also fulfilled the criteria for LFL or LFS. All families had previously been found negative for germline BRCA1, BRCA2 and TF53 mutations , together explaining about 23% of hereditary predisposition to breast canc er in our country. Only one missense-type mutation, Ile(157) --> Thr(157), was detected. The high Ile(157) --> Thr(157) mutation frequency (6.5%) obse rved in healthy controls and the lack of other mutations suggest that CHK2 does not contribute significantly to the hereditary breast cancer or LFL-as sociated breast cancer risk, at least not in the Finnish population. For Il e(157)-->Thr(157) our result deviates from what has been reported previousl y. (C) 2001 Cancer Research Campaign http://www.bjcancer.com.