<i>BRCA1</i> Mutations in Primary Breast and Ovarian Carcinomas

TLDR

Loss of heterozygosity in familial and sporadic breast and ovarian cancers implicates BRCA1 as a tumor‑suppressor gene whose mutations confer susceptibility to early‑onset disease. The authors screened the BRCA1 coding sequence in primary breast and ovarian tumors exhibiting allele loss at the BRCA1 locus. Germline BRCA1 mutations were found in 3 of 32 breast and 1 of 12 ovarian carcinomas, indicating that BRCA1 mutation is not essential for most sporadic breast and ovarian cancers lacking a germline allele.

Abstract

Loss of heterozygosity data from familial tumors suggest that BRCA1 , a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors 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 results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele.