Navigating the DNA methylation landscape of cancer

Atsuya Nishiyama; Makoto Nakanishi

doi:10.1016/j.tig.2021.05.002

Navigating the DNA methylation landscape of cancer

Trends Genet. 2021 Nov;37(11):1012-1027. doi: 10.1016/j.tig.2021.05.002. Epub 2021 Jun 10.

Authors

Atsuya Nishiyama¹, Makoto Nakanishi²

Affiliations

¹ Division of Cancer Cell Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Electronic address: uanishiyama@g.ecc.u-tokyo.ac.jp.
² Division of Cancer Cell Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Electronic address: mkt-naka@g.ecc.u-tokyo.ac.jp.

PMID: 34120771
DOI: 10.1016/j.tig.2021.05.002

Abstract

DNA methylation is a chemical modification that defines cell type and lineage through the control of gene expression and genome stability. Disruption of DNA methylation control mechanisms causes a variety of diseases, including cancer. Cancer cells are characterized by aberrant DNA methylation (i.e., genome-wide hypomethylation and site-specific hypermethylation), mainly targeting CpG islands in gene expression regulatory elements. In particular, the early findings that a variety of tumor suppressor genes (TSGs) are targets of DNA hypermethylation in cancer led to the proposal of a model in which aberrant DNA methylation promotes cellular oncogenesis through TSGs silencing. However, recent genome-wide analyses have revealed that this classical model needs to be reconsidered. In this review, we will discuss the molecular mechanisms of DNA methylation abnormalities in cancer as well as their therapeutic potential.

Keywords: DNA methylation; DNA methyltransferase; cancer; histone modification.

Publication types

Review

MeSH terms

CpG Islands / genetics
DNA Methylation* / genetics
Genome-Wide Association Study
Humans
Neoplasms* / genetics
Neoplasms* / metabolism