Epigenetic regulation of the cell cycle & DNA-repair in cancer

Abstract The human genome's spectrum of gene expression patterns is vast and, while constantly adapting to surrounding cues, versatile and variable. It generates hundreds of different cell types forming multiple tissues and organ systems [1], amongst which well over a hundred cancer types have been identified to date [1]. While originating from the same ancestor, thereby harboring nearly identical genetic information, every eukaryotic cell type presents with its own distinguishable biological behavior and phenotype, underscoring the degree of cell plasticity inherent during development. Instead of being established by DNA sequence alterations, the rich diversity of cell identities is now thought to be defined and largely driven by epigenetic variation—a regulatory engine fueled by the homeostatic balance of chromatin regulators and designed to maintain physiological organismal homeostasis to ensure functional gene expression in both stressful and quiescent situations. Disruption of chromatin homeostasis results in it becoming either aberrantly restrictive or aberrantly permissive, thereby driving tumor initiation in pre-malignant cells and/or tumor evolution and adaptation in malignant cells. Hence, epigenetic instability may represent the 11th hallmark of cancer—both as a cause and consequence of, or even without concomitant genomic instability.