title: Mutation analysis of the CHK2 gene in families with hereditary breast cancer.
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.
authors.affiliation: Department of Clinical Genetics, University of Oulu/Oulu University Hospital, Oulu, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Allinen
authors.forename: P
authors.initials: P
authors.lastname: Huusko
authors.forename: S
authors.initials: S
authors.lastname: Mäntyniemi
authors.forename: V
authors.initials: V
authors.lastname: Launonen
authors.forename: R
authors.initials: R
authors.lastname: Winqvist
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D064447:Checkpoint Kinase 2; D015331:Cohort Studies; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D010375:Pedigree; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases
chemical_list: D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases