Epigenetic dysregulation and cancer evolution: a network perspective

The complex network of proteins that regulate chromatin and DNA methylation landscapes is often disrupted in cancer. Clonal and subclonal mutations targeting a wide range of molecular functions are frequently observed across cancer types, and emerging evidence suggests that loss of robust epigenetic control promotes both cancer initiation and evolution, independently of context-specific effects. I will discuss how diverse genetic alterations that destabilize the epigenetic regulatory network converge into common phenotypes that confer a selected advantage to the affected cells. I will also discuss the implications of altered network topology and systemic epigenetic disorder for the evolution, vulnerability, and therapeutic resistance of cancers.