Mutations of the BRCA1 gene in tumor DNA from patients with sporadic b
reast 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 brea
st carcinomas but not in any normal tissues, The hypermethylation was
not an artifact because a control region was unmethylated in the two t
umors. Although not all tumors were hypermethylated, these observation
s are consistent with an important role for epigenetic mechanisms in h
uman cancer.