The tubal epigenome – An emerging target for ovarian cancer

Abstract Ovarian cancer is the most lethal gynecologic malignancy in the United States. The mortality of this disease is primarily attributed to challenges in early detection and therapeutic resistance. Recent studies indicate that the majority of high-grade serous ovarian carcinomas (HGSCs) originate from aberrant fallopian tube epithelial (FTE) cells. This shift in thinking about ovarian cancer pathogenesis has been met with an effort to identify the early genetic and epigenetic changes that underlie the transformation of normal FTE cells and prompt them to migrate and colonize the ovary, ultimately giving rise to aggressive HGSC. While identification of these early changes is important for biomarker discovery, the emergence of epigenetic alterations in FTE chromatin may also provide new opportunities for early detection, prevention, and therapeutic intervention. Here we provide a comprehensive overview of the current knowledge regarding early epigenetic reprogramming that precedes HGSC tumor development, the way that these alterations affect both intrinsic and extrinsic tumor properties, and how the epigenome may be targeted to thwart HGSC tumorigenesis.