Methylation of the BRCA1 gene in sporadic breast cancer.

Mutations of the BRCA1 gene in tumor DNA from patients with sporadic breast cancer have not yet been observed. Nevertheless, BRCA1 activity is markedly decreased in invasive breast tumors. Previous reports have shown that hypermethylation of the promoter region is an alternative mechanism to mutation for the inactivation of tumor suppressor genes. We examined the BRCA1 promoter region for hypermethylation by Southern blotting. Hypermethylation was observed in two of seven sporadic breast carcinomas but not in any normal tissues. The hypermethylation was not an artifact because a control region was unmethylated in the two tumors. Although not all tumors were hypermethylated, these observations are consistent with an important role for epigenetic mechanisms in human cancer.