Cancer epigenetics: DNA methylation and chromatin alterations in human cancer

Abstract

Aberrations in the DNA methylation patterns are nowadays recognized as a hallmark of human cancer. One of the most characteristic changes is the hypermethylation of CpG islands of tumor suppressor genes associated with their transcriptional silencing. The target genes are distributed in all cellular pathways (apoptosis, DNA repair, cell cycle, cell adherence, etc.). They are "classical" tumor suppressor genes with associated familial cancers (BRCA1, hMLH1, p16INK4a, VHL, etc.) and putative new tumor suppressor genes which loss may contribute to the transformed phenotype (MGMT, p14ARF, GSTP1, RARB2, etc.). A tumor-type specific profile of CpG island hypermethylation exist in human cancer that allows the use of these aberrantly hypermethylated loci as biomarkers of the malignant disease. The eruption of new technologies for the careful study of the DNA methylation patterns, and their genetic partners in accomplishing gene silencing, it may also provide us with new drugs for the epigenetic treatment of human tumors.