BRCA2 germline mutations in male breast cancer cases and breast cancer families

The breast cancer susceptibility gene, BRCA2 on chromosome 13q12–13, was recently isolated1–3. Mutations in BRCA2 are thought to account for as much as 35% of all inherited breast cancer as well as a proportion of inherited ovarian cancer1. Many BRC2-linked families also contain cases of male breast cancer. We have analysed germline DMA from 50 males with breast cancer (unselected for family history) and 26 individuals from site-specific female breast and breast–ovarian cancer families for mutations in BRCA2. All 17 breast–ovarian cancer families have been screened for BRCA1 coding region mutations and none were detected. Conformation-sensitive gel electrophoresis (CSGE) analysis of PCR-amplifed DMA followed by direct sequencing was used to detect sequence variants. Three of eleven individuals carry the same mutation, all are of Ashkenazi Jewish descent, supporting the observation by Neuhausen et al, in this issue4 that there is a common mutation in this population. Eleven truncating mutations and nine polymorphisms were identified — all were coding region variants. No loss-of-transcript mutations were identified in the sixteen samples for which this analysis was possible. Seven of the nine disease-associated mutations were detected in the 50 men with breast cancers; thus in our series, BRCA2 mutations account for 14% of male breast cancer, all but one of which had a family history of male and/or female breast cancer.