DNA demethylation and cancer: therapeutic implications.
The epigenome, which is comprised of chromatin and its associated proteins and the patterns of covalent modification of DNA by methylation, sets up and maintains gene expression programs. A hallmark of cancer is a paradoxical aberration of DNA methylation patterns, a global loss of DNA methylation, that coexists with regional hypermethylation of certain genes. The hypermethylation of tumor-suppressor genes has attracted significant attention recently and DNA methylation inhibitors are being tested as potential anticancer agents. However, emerging data suggests that hypomethylation plays a role in activating genes required for metastasis and invasion. It is proposed here that hypermethylation and hypomethylation in cancer are independent processes, which target different programs at different stages in tumorigenesis. Understanding the relative roles of hypomethylation and hypermethylation in cancer has clear implications on the therapeutic use of agents targeting the DNA methylation machinery, which are discussed in this review.
Szyf
Moshe
M
Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Que., Canada PQ H3G 1Y6. moshe.szyf@mcgill.ca
Pakneshan
Pouya
P
Rabbani
Shafaat A
SA
D001943:Breast Neoplasms / Q000235:genetics / Q000503:physiopathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006657:Histones; D006801:Humans; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*
D004273:DNA, Neoplasm; D006657:Histones