PITCHER (Peritoneal Carcinomatosis Heterogeneity)

How epigenetic deregulation affects gene expression patterns in subclones of the same tumor is poorly known. Peritoneal Carcinomatosis (PC) is a condition in which multiple metastases of the same abdominal tumor develop in the peritoneal cavity and intra-peritoneal organs, thus defining different ecosystems of the same cancer. PITCHER addresses the variations in epigenetically regulated gene expression between different subclones of PC in relation with cell mechanoresponses, providing insights on how cancer epigenetic landscapes evolve under environmental pressures and on strategies used by cancer cells to adapt to the transition from one ecosystem to the other. PITCHER is a network of 10 teams from Lyon, Grenoble and Marseille, based on data and specimen collection of patients who have undergone a surgery for a peritoneal carcinomatosis of ovarian or colorectal origin. PC lesions and eventually matched specimens of primary tumors will be collected in the same patients at the time of the surgery or eventually retrieved from already existing samples. Epigenetic landscapes will be analyzed by a bioinformatics pipeline combining exome sequencing, transcriptome and methylome to identify "epigenetic hotspots", and their variations across lesions will be evaluated. These analyses will be realized in fresh (when available) or pre-existing samples. When possible, organoid cultures and animal models will be derived from multicellular structures in peritoneal fluids and membrane, cytoskeletal and nucleoskeletal mechanoresponses will be characterized using Atomic Force Microscopy. The role of tumor axonogenesis, a process of neo-formation of axon fibers in tumors, will be addressed. Experimental studies of cell responses to therapy will be performed to derive mathematical predictive models. All components will be integrated in a systems biology map of PC.