The epigenetics of (hereditary) colorectal cancer

In the last decade, it has become apparent that not only DNA sequence variations but also epigenetic modifications may contribute to disease, including cancer. These epigenetic modifications involve histone modification including acetylation and methylation, DNA methylation, and chromatin remodeling. One of the best-characterized epigenetic changes is aberrant methylation of cytosines that occur in so-called CpG islands. DNA hypomethylation, prevalent as a genome-wide event, usually occurs in more advanced stages of tumor development. In contrast, DNA hypermethylation is often observed as a discrete, targeted event within tumor cells, resulting in specific loss of gene expression. Interestingly, it was found that sporadic and inherited cancers may exhibit similar DNA methylation patterns, and many genes that are mutated in familial cancers have also been found to be hypermethylated, mutated, or deleted in sporadic cancers. In this review, we will focus on DNA methylation events as heritable epimutations predisposing to colorectal cancer development.