DNA Methylation and Cancer英文文献.pdfVIP

2 DNA Methylation and Cancer Marta Kulis and Manel Esteller Cancer Epigenetics and Biology Program (PEBC), The Bellvitge Institute for Biomedical Research (IDIBELL), Hospital Duran i Reynals, Avinguda Gran Via de L’Hospitalet 199-203, E-08907 L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain I. Introduction II. The Molecular Basis of DNA Methylation III. DNA Methylation Abnormalities in Cancer A. DNA hypomethylation B. DNA hypermethylation IV. DNA Methylation Markers V. Determining the Cancer DNA Methylome VI. Therapy Perspectives VII. Conclusions References ABSTRACT DNA methylation is one of the most intensely studied epigenetic modifications in mammals. In normal cells, it assures the proper regulation of gene expression and stable gene silencing. DNA methylation is associated with histone modifica- tions and the interplay of these epigenetic modifications is crucial to regulate the functioning of the genome by changing chromatin architecture. The covalent addition of a methyl group occurs generally in cytosine within CpG dinucleo- tides which are concentrated in large clusters called CpG islands. DNA methyl- transferases are responsible for establishing and maintenance of methylation pattern. It is commonly known that inactivation of certain tumor-suppressor Advances in Genetics, Vol. 70 0065-2660/10 $35.00 Copyright 2010, Elsevier Inc. All rights reserved. DOI: 10.1016/S0065-2660(10)70002-X 28 Kulis and Esteller genes occurs as a consequence of hypermethylation within the promoter regions and a numerous studies have demonstrated a broad range of genes silenced by DNA methylation in different cancer types. On the