BRCA1 mutations in familial ovarian cancer

BRCA1 mutation research in ovarian and breast cancer 17q21-linked families has yielded a large number of germline sequence variations. Somatic mutatio ns have been uncommonly reported. We screened 81 probands with primary ovar ian, peritoneal, or fallopian tube carcinoma for BRCA1 mutations. The study group was intentionally biased by the inclusion of 29 probands with a fami ly history of ovarian and/or breast carcinoma, 13 probands diagnosed on or before age 45, seven individuals with a metachronous breast cancer and 51 t umors with BRCA1 LOH. Tumor and/or germline DNA was screened by modified te chniques of single-strand confirmation polymorphism analysis, and abnormal banding patterns were sequenced to confirm mutations. Twenty-one (25.9%) BR CA1 sequence variations were identified. Eight mutations were somatic inclu ding seven null mutations. Apart from classical hereditary ovarian/breast c ancer, a family history of ovarian/breast cancer de fines a subset of ovari an cancer individuals with a significant likelihood of either a germline or a somatic BRCA1 gene sequence variation. (C) 1999 Academic Press.