BRCA1 MUTATIONS IN PRIMARY BREAST AND OVARIAN CARCINOMAS

Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast ca ncer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication tha t BRCA1 mutations may occur somatically in these tumors. The BRCA1 cod ing region was examined for mutations in primary breast and ovarian tu mors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These r esults suggest that mutation of BRCA1 may not be critical in the devel opment of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele.