MUTATIONS AND POLYMORPHISMS IN THE FAMILIAL EARLY-ONSET BREAST-CANCER(BRCA1) GENE

Mutations in the familial early-onset breast cancer gene (BRCA1) accou nt for approximately 2-5% of all breast cancer cases (Easton et al., 1 993). Since the isolation of the BRCA1 gene in 1994, many mutations ha ve been identified. We report here a total of 254 BRCA1 mutations, 132 (52%) of which are unique. These represent mutations entered into a d atabase established by the Breast Cancer Information Core (BIC), which have appeared in the literature or have been submitted by BIC members and other contributors prior to publication. A total of 221 (87%) of all mutations or 107 (81%) of the unique mutations are small deletions , insertions, nonsense point mutations, splice variants, and regulator y mutations that result in truncation or absence of the BRCA1 protein. A total of 11 disease-associated missense mutations (5 unique), and 2 1 variants (19 unique) as yet unclassified as either missense mutation s or polymorphisms have been detected. Thirty-five independent benign polymorphisms are also described. The most common mutations are 185del AG and 5382insC, which account for 30 (11.7%) and 26 (10.1%), respecti vely, of all mutations shown. The biological and clinical relevance of these BRCA1 mutations is discussed. (C) 1996 Wiley-Liss, Inc.