Guardians of cell identity Functional analysis of PRC2 proteins in intestinal homeostasis and cancer

This thesis aims to better understand how the Polycomb Group of epigenetic repressors contribute to homeostasis of adult tissue, how their dysregulation can drive cancer and whether this may present a weakness for tumors. The experimental work presented in this thesis is focused on PRC2 and its actions in normal and cancerous tissue of the gastrointestinal tract as well as in prostate cancer development. By using mouse models and intestinal organoid cultures followed by analysis of genome-wide mutation and transcription profiles we discovered novel connections of PRC2 activity with pathways underpinning intestinal homeostasis as well as mutations in colorectal cancer. The latter may be used to predict patient response to therapy with inhibitors of PRC2.