Thus, a majority of these patients lack any known genetic marker. Our aim was to explore the relevance of BRCA mutations to serve as such markers in the genetic screening and counseling of CRC patients. No carriers were found among the Arabs and non-Ashkenazi Jews surveyed. Inherited mutations in the BRCA1 gene may be responsible for almost half of inherited breast carcinomas. To address whether BRCA1 may be inactivated by pathways other than mutations in sporadic tumors, we analyzed the role of hypermethylation of the gene's promoter region.
P values are two-sided.
The BRCA1 promoter was found to be unmethylated in all normal tissues and cancer cell lines tested. However, BRCA1 promoter hypermethylation was present in two breast cancer xenografts, both of which had loss of the BRCA1 transcript. The BRCA1 promoter was unmethylated in other tumor types. Silencing of the BRCA1 gene by promoter hypermethylation occurs in primary breast and ovarian carcinomas, especially in the presence of LOH and in specific histopathologic subgroups. These findings support a role for this tumor suppressor gene in sporadic breast and ovarian tumorigenesis.