Cancer Epigenetics

1. Cancer Epigenetics Epigenetics is the study of heritable changes in gene function that do not involve changes in the DNA sequence. A variety of epigenetic mechanisms can be perturbed in different types of cancer. Epigenetic alterations of DNA repair genes or cell cycle control genes are very frequent in sporadic (non-germ line) cancers, being significantly more common than germ line (familial) mutations in these sporadic cancers. So researchers think that epigenetic alterations may be just as important, or even more worthy, than genetic mutations in a cell's transformation to cancer. So far, the mechanisms of epigenetic is the covalent modifications(covalent modifications of either DNA (e.g. cytosine methylation(CpG) and hydroxymethylation) or of histone proteins (e.g. lysine acetylation, lysine and arginine methylation, serine and threonine phosphorylation, and lysine ubiquitination and sumoylation).), RNA transcripts(include: recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci; the production of different splice forms of RNA; formation of double-stranded RNA (RNAi)), MicroRNAs, the modification of mRNA, sRNAs, Prions and so on. In cancers, loss of expression of genes occurs about 10 times more frequently by transcription silencing (caused by epigenetic promoter hypermethylation of CpG islands) than by mutations. As Vogelstein et al. point out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa. Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. Several medications which have epigenetic impact are now employed in several of these diseases.