MUTATIONS IN THE BRCA1 GENE IN JAPANESE BREAST-CANCER PATIENTS

Predisposing germline mutations in the BRCA1 gene were identified rece ntly in families with 17q-linked breast and ovarian cancers. Using sin gle-strand conformation polymorphism (SSCP) analysis, we examined prim ary breast cancers for mutations in coding exons of BRCA1 in a panel o f 103 patients, of whom all either represented early-onset cases (<35 of age), were members of multiply-affected families, and/or had develo ped bilateral breast cancers. Mutations were detected in tumors from f our patients, all of whom had developed breast cancers bilaterally: a frame-shift due to a 2-bp deletion at codon 797; a nonsense mutation a t codon 1214; and two missense mutations, one at codon 271 leading to Val --> Met substitution, and the other at codon 1150 leading to Pro - -> Ser substitution. In each case the same mutation was present in con stitutional DNA. The mean age of onset was 49 years among the Japanese carriers of BRCA1 mutations identified in this study, in contrast to the mean age of 35 observed among carriers of BRCA1 mutations in a sim ilar U.S. study (Futreal et al., 1994). The evidence reported here sup ports a rather limited role of BRCA1 in breast carcinogenesis. (C) 199 6 Wiley-Liss, Inc.