How to stomach an epigenetic insult: the gastric cancer epigenome

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Abstract

Gastric cancer is a deadly malignancy and accumulating evidence suggests that epigenetic abnormalities promote carcinogenesis. Here, the authors summarize the gastric cancer epigenome, highlighting key advances from studies of DNA methylation and histone modifications, and how these findings might lead to therapeutic opportunities.

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Gene body methylation can alter gene expression and is a therapeutic target in cancer.

Xiaojing Yang, Han Han, Daniel De Carvalho … (2014)

DNA methylation in promoters is well known to silence genes and is the presumed therapeutic target of methylation inhibitors. Gene body methylation is positively correlated with expression, yet its function is unknown. We show that 5-aza-2'-deoxycytidine treatment not only reactivates genes but decreases the overexpression of genes, many of which are involved in metabolic processes regulated by c-MYC. Downregulation is caused by DNA demethylation of the gene bodies and restoration of high levels of expression requires remethylation by DNMT3B. Gene body methylation may, therefore, be an unexpected therapeutic target for DNA methylation inhibitors, resulting in the normalization of gene overexpression induced during carcinogenesis. Our results provide direct evidence for a causal relationship between gene body methylation and transcription. Copyright © 2014 Elsevier Inc. All rights reserved.