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Epigenetics. 2017 Jun 3;12(6):416-432. doi: 10.1080/15592294.2017.1311434. Epub 2017 Mar 30.

DNA methylation aberrancies as a guide for surveillance and treatment of human cancers.

Author information

1
a Department of Urology , University of Southern California, USC Norris Comprehensive Cancer Center , Los Angeles , CA , USA.
2
b Department of Biochemistry and Molecular Medicine , University of Southern California, USC Norris Comprehensive Cancer Center , Los Angeles , CA , USA.

Abstract

DNA methylation aberrancies are hallmarks of human cancers and are characterized by global DNA hypomethylation of repetitive elements and non-CpG rich regions concomitant with locus-specific DNA hypermethylation. DNA methylation changes may result in altered gene expression profiles, most notably the silencing of tumor suppressors, microRNAs, endogenous retorviruses and tumor antigens due to promoter DNA hypermethylation, as well as oncogene upregulation due to gene-body DNA hypermethylation. Here, we review DNA methylation aberrancies in human cancers, their use in cancer surveillance and the interplay between DNA methylation and histone modifications in gene regulation. We also summarize DNA methylation inhibitors and their therapeutic effects in cancer treatment. In this context, we describe the integration of DNA methylation inhibitors with conventional chemotherapies, DNA repair inhibitors and immune-based therapies, to bring the epigenome closer to its normal state and increase sensitivity to other therapeutic agents to improve patient outcome and survival.

KEYWORDS:

Cancer; DNA demethylation; DNA methylation; DNA methylation inhibitors and epigenetic therapy; DNA methyltransferase; TET; chromatin; histone modification

PMID:
28358281
PMCID:
PMC5501209
DOI:
10.1080/15592294.2017.1311434
[Indexed for MEDLINE]
Free PMC Article

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