Whole exome sequencing on one human ascites, cultured ovarian cancer cells, blood sample and ascites from patient-derived xenograft.

Epithelial ovarian cancer (EOC) is the most lethal gynecological tumor in developed countries. High-grade serous ovarian carcinoma (HGSOC) is the frequent and intractable form of EOC, mainly due to its rapid dissemination into the abdominal cavity, a process that is tightly linked to peritoneal ascites. The precise molecular alterations involved in HGSOC onset and progression remain largely unknown due to its very high biological and genetic heterogeneity. To tackle the issue, we derived matched tumor samples consisting in HGSOC ascites, primary tumor cells, OCSC-enriched spheroids and serially propagated patient-derived xenografts, to explore the molecular alterations relevant in metastasis and ovarian cancer stem cells (OCSC). We defined genetic and transcriptional signatures associated to specific HGSOC evolutionary trajectories. Such signatures exhibited prognostic value in a large cohort of HGSOC patients and allowed to define PI3K signaling as a novel vulnerability in OCSCs.