VIEWS IN THE SPOTLIGHT BRCA1: A Missing Link in the Fanconi

Summary: Domchek and colleagues provide a case report of a 28-year-old woman with congenital abnormalities, inherited ovarian cancer, and carboplatin hypersensitivity. Interestingly, the woman had validated germline muta-tions in both BRCA1 alleles. These fi ndings further implicate BRCA1 in the Fanconi anemia/BRCA pathway and have important implications for BRCA1 genetic testing. Cancer Discov; 3(4); 376–8. ©2013 AACR. See related article by Domchek et al., p. 399 (6). Signifi cant advances in our understanding of breast and ovarian cancer have resulted from the genetic link-age mapping and cloning of 2 major tumor suppressor genes, BRCA1 and BRCA2. Mutations in BRCA1 and BRCA2 account for approximately 16 % of the familial risk of breast cancer ( 1). Moreover, heterozygous carriers of mutations in BRCA1 and BRCA2 have an 82 % lifetime risk of breast cancer and a 54 % and 23 % risk of ovarian cancer, respec-tively ( 2). Biallelic germline mutations in BRCA2 account for a rare and highly cancer-prone subtype of Fanconi ane