Mutation unalysis of the BRCA1 gene in familial and sporudic breast cancer

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Predisposing mutations in a BRCA1 gene have been recently identified in 17-9 linked breast and ovarian cancer families. We examined breast cancers consisting of 46 early-onse cases (<35 of age), 12 cases with familial clustering, and 59 bilateral cancers for mutations ir entire coding exons of BRCA1 gene using single strand conformation polymorphism (SSCP) analysis. Four mutaions were detected in this panel of 103 patients ; a flame-shift due to 2-bp deletion at codon 797, a nonsense mutation at codon 1214, two missense mutations, one at codon 271 leading to Val->Met substitution, and the other at codon 1150 leading to Pro->Ser substitution. All of them were germiline mutations ; no somatic mutation were found in these tumors, a finding that support a rather confined role of BRCA1 in breast carcinogenesis. Among the three selection groups, all four mutations were found in patients with bilateral tumors. It therefore appears that bilaterality is a prominent phenotypic halmark of BRCA1 p … More redisposition. These results provide informations for understanding the role of BRCA1 gene mutation in familial forms of breast tumors and will contribute to genetic counseling and presymtomatic diagnosis of members in breast cancer families.To better understand the frequency, distribution and nature of BRCA1 mutations Japanese breast cancer patients, we screened 1,000 unselected primary cancers f mutations in exon 11, which accounts for 61% of the entire BRCA1 coding sequence. Using method based on multiplex single-strand conformational polymorphism (SSCP) analysis multiple restriction fragments generated by restriction-enzyme digestion of amplified DNA,w identified eight mutations including four that we had previously found in a subset of thes cases. All eight were germline mutations ; four of them were non-sense mutations or sma deletions resulting in premature stop codons, and the other four were missense mutation. The Japanese carriers of these mutant BRCA1 alleles had developed breast cancers at age ranging from 45 to 62, five of them bilaterally. Taking into account the effect of various facto such as life-time risk of breast cancer, screening efficiency, and the region examined, w roughly estimate that 2-3 % of breast cancer in Japan is attributable to BRCA1 mutation ar that 1 in 1,500-2,000 Japanese women carry a germline mutation in the BRCA1 gene. Less