DNA Methylation in Epithelial Ovarian Cancer: Current Data and Future Perspectives

Abstract

Ovarian cancer is an aggressive disease, and only a few cases are diagnosed at early stages due to the absence of symptoms. Τhe majority of malignant ovarian tumors (>90%) are of epithelial origin and are subdivided into five histological sub types according to different molecular pathogenesis and clinical behavior. High-grade serous ovarian cancer is the most common subtype (70%). However, the different histotypes of ovarian cancer should be viewed as separate diseases both clinically and in biomarker studies. At present, surgical debulking and platinum/taxane - based chemotherapy is the standard of care for epithelial ovarian cancer. Most patients show an initial response to this therapeutic approach, but the majority of them experience disease recurrence at which point cure is no longer possible, due to acquired resistance in those chemotherapeutic regimens. Nevertheless, the current treatment model is still a "one-sizefits- all" approach. Epigenetic modifications represent heritable modifications in gene expression without alteration of the DNA sequence. DNA methylation is the best-studied epigenetic mechanism, and in epithelial ovarian cancer, the methylenome is widely altered. In addition, patterns of DNA methylation may represent potential diagnostic and prognostic markers as well as markers predictive of chemoresistance and potential therapeutic targets. This article systematically reviews the complex area of DNA methylation in ovarian carcinoma and summarizes the current implications and future perspectives of its use as a screening, diagnostic, prognostic and predictive tool as well as in personalized cancer therapy.

Keywords: DNA methylation; Ovarian carcinoma; epigenetics; high-grade serous carcinoma; methylenome; therapyresistance..