Cancer epigenomics: DNA methylomes and histone-modification maps

Top Cited Papers
Publisher Website
Google Scholar
Abstract
During the past two decades, an increasing amount of experimental data has been gathered that support the idea that epigenetic alterations, particularly DNA methylation and histone modifications, have a crucial role in the development and progression of human cancer. The epigenetic silencing of tumour-suppressor genes by CpG-island-promoter hypermethylation has emerged as a driving force in tumorigenesis. Further investigations are required to understand the contributions of genomic DNA hypomethylation and altered histone-modification signatures in human tumours. Epigenetic research is moving on from candidate-gene approaches towards genome-wide analyses, on the basis of the combination of new techniques combining bisulphite treatment and PCR, new antibodies against epigenetic marks and the epigenetic machinery, and high-resolution microarray platforms. These new epigenomic analyses show a profound disruption of the epigenetic modifications of cancer cells, with a large number of genes undergoing methylation-associated silencing, a global change in the acetylation and methylation profiles of histones, and aberrations in the genes responsible for the maintenance of normal chromatin structure. Epigenomic technologies have promising translational applications for human cancer, with potential for early diagnosis, prognosis and clinical management, particularly in the young field of pharmacoepigenetics. Our knowledge of cancer epigenetics will benefit greatly from the development of ambitious whole-genome endeavours, such as the international consortia that have been set up for the analysis of complete human and model-organism epigenomes.