BRCA1 and BRCA2 are tumor suppressor genes that play important roles in cellular functioning such as DNA damage repair. Mutations in these genes have been associated with 5% to 10% of epithelial ovarian cancers. Whether BRCA1 and BRCA2 mutations lead to cancer through similar or different pathways is unclear. A past study of BRCA1 and BRCA2-linked breast cancers revealed distinct differences in gene expression patterns between the two types of mutations.

To determine whether genetic differences also exist in BRCA-linked ovarian cancers, Amir A. Jazaeri, M.D., and Edison T. Liu, M.D., of the National Cancer Institute and their colleagues compared gene expression patterns of tumors from 18 ovarian cancer patients with BRCA1 mutations, 16 patients with BRCA2 mutations, and 27 patients with sporadic ovarian cancers.

The authors found that overall patterns of gene expression differed between the BRCA1-associated and BRCA2-associated tumors. Of the roughly 6,500 genes analyzed, 110 were found to be different between BRCA1- and BRCA2-associated tumors. However, the authors discovered that the same genes whose expression separated BRCA1-associated and BRCA2-associated tumors also identified two major groups of sporadic cancers.

"The observation that BRCA-associated gene expression profiles are recapitulated in major subsets of sporadic tumors suggests that molecular mechanisms common to both hereditary and sporadic ovarian carcinogenesis exist," the authors conclude.

In an accompanying editorial, Ingrid A. Hedenfalk, Ph.D., of the National Human Genome Research Institute at the National Institutes of Health, says a possible explanat
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Contact: Linda Wang
jncimedia@oupjournals.org
301-841-1287
Journal of the National Cancer Institute
2-Jul-2002