BRCA2 mutations in primary breast and ovarian cancers.
The second hereditary breast cancer gene, BRCA2, was recently isolated. Germline mutations of this gene predispose carriers to breast cancer, and, to a lesser extent, ovarian cancer. Loss of heterozygosity (LOH) at the BRCA2 locus has been observed in 30-40% of sporadic breast and ovarian tumours, implying that BRCA2 may act as a tumour suppressor gene in a proportion of sporadic cases. To define the role of BRCA2 in sporadic breast and ovarian cancer, we screened the entire gene for mutations using a combination of techniques in 70 primary breast carcinomas and in 55 primary epithelial ovarian carcinomas. Our analysis revealed alterations in 2/70 breast tumours and none of the ovarian carcinomas. One alteration found in the breast cancers was a 2-basepair (bp) deletion (4710delAG) which was subsequently shown to be a germline mutation, the other was a somatic missense mutation (Asp3095Glu) of unknown significance. Our results suggest that BRCA2 is a very infrequent target for somatic inactivation in breast and ovarian carcinomas, similar to the results obtained for BRCA1.
Lancaster, JM; Wooster, R; Mangion, J; Phelan, CM; Cochran, C; Gumbs, C; Seal, S; Barfoot, R; Collins, N; Bignell, G; Patel, S; Hamoudi, R; Larsson, C; Wiseman, RW; Berchuck, A; Iglehart, JD; Marks, JR; Ashworth, A; Stratton, MR; Futreal, PA
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