Epimutations and cancer predisposition: importance and mechanisms

Germline sequence mutations in tumour suppressor genes can cause cancer predisposition syndromes. More recently, epimutations have also been proposed to cause at least one such syndrome, hereditary non-polyposis colorectal cancer (HNPCC). ‘Epigenetic predisposition’, is defined as an inherited propensity to an altered epigenetic state in normal tissues that confers a predisposition to disease. Genetic sequence variations acting in cis or trans may contribute to epigenetic variations. Understanding the origin of epimutations will inform cancer risk assessment and will also aid the design and application of new therapies that target the epigenome.