Abstract 2417: Large scale integrated transcriptomic and epigenetic profiling defines the molecular hallmarks of HGSOC and disease origins

High-grade serous ovarian cancers (HGSOCs) are the most common subtype of epithelial ovarian cancer. Pathways driving HGSOC development are poorly understood, and the cellular origins are debated in the literature. Previously, ovarian surface epithelial cells (OSECs) were thought to be cellular precursors of HGSOC, but there is now strong evidence that at least half of all HGSOCs arise from fallopian tube secretory epithelial cells (FTSECs). We took a large-scale integrated transcriptomic-epigenomic profiling approach to defining the molecular hallmarks of HGSOC and to explore the disease cell-of-origin. RNA sequencing was performed on 121 OSEC cultures and 84 FTSEC cultures and integrated with 394 HGSOC transcriptomes profiled by TCGA. We identified around 100 genes that differentiate OSECs and FTSECs, and pathway analysis of this gene list identified ovarian cancer genes as highly enriched (p=2.2x10-8), with ZEB1 and estrogen the most significant predicted upstream regulators (P Citation Format: Kate Lawrenson, Marcos Abraao, Felipe Segato, Janet M. Lee, Simon Coetzee, Ji-Heui Seo, Matthew L. Freedman, Dennis Hazelett, Simon Gayther, Houtan Noushmehr. Large scale integrated transcriptomic and epigenetic profiling defines the molecular hallmarks of HGSOC and disease origins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2417. doi:10.1158/1538-7445.AM2017-2417