Epigenetic alteration of BRCA1 in human ovarian tumors

Abstract

e16532 Background: The breast cancer susceptibility gene 1 (BRCA1) is mutated in half of hereditary breast cancers, and in about 80% of hereditary breast and ovarian cancers. Also, BRCA1 expression is decreased in sporadic breast cancers by other mechanisms, such as epigenetic alteration, suggesting its important role in sporadic breast cancers. The epigenetic alteration of BRCA1 and its contribution in sporadic ovarian tumors are not fully understood. Methods: We evaluated the DNA methylation status of the BRCA1 5’ CpG island by methylation-specific PCR in 12 human ovarian cancer cell lines and 39 primary epithelial ovarian tumor specimens. Cases included the following: malignant (n = 16), borderline (n = 8), and benign (n = 16) tumors. The correlation between these results and clinicopathological features was examined. Results: BRCA1 was hypermethylated in one of 12 (8%) ovarian cancer cell lines and 15 of 39 (38%) primary ovarian tumors. Relative to clinicopathological features, BRCA1 methylation was detected in 39% of malignant and borderline tumors and in 38% of benign tumors, suggesting the importance of BRCA1 pathway in both types of tumors. Some adjacent nontumorous tissues also showed aberrant methylation. Conclusions: BRCA1 was found to be frequently hypermethylated both in benign and malignant ovarian tumors. Our results suggest that epigenetic alteration of BRCA1 might play a role in the development of benign and malignant sporadic ovarian tumors. No significant financial relationships to disclose.