A critical re-appraisal of BRCA1 methylation studies in ovarian cancer

A central challenge facing gynecologic oncology is achieving personalized care in ovarian cancer treatment. The current ovarian cancer classification scheme distinguishes tumors based on histopathologic subtype, grade, and surgical stage. Recent molecular investigations have highlighted distinguishing genetic features of certain tumors within a given category, and given the rapid pace of technologic advancement combined with plummeting costs for complete genomic sequencing this classification will markedly improve. Clinical studies have begun to explore the influence of currently known distinctions on the natural history of the disease, most recently with particular attention to the BRCA1 status of tumors. Mutations in the BRCA1 gene have long been known to increase a woman's risk of developing ovarian cancer. As has been shown, BRCA1-associated ovarian cancers may be associated with characteristic differences in therapeutic response and overall survival, and further defining these subsets may become instrumental in clinical decision-making. Therefore, given the eightfold difference (5-40%) in reported frequency of BRCA1 inactivation by methylation in the pioneering studies in the field, a critical re-appraisal of the literature, techniques, samples used, and interpretations of BRCA1 inactivation is warranted along with a review of the more recent and comprehensive molecular studies.