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DNA methylation and gene silencing in cancer

Nature Clinical Practice Oncology volume 2, pages S4–S11 (2005)Cite this article

Abstract

Epigenetic changes such as DNA methylation act to regulate gene expression in normal mammalian development. However, promoter hypermethylation also plays a major role in cancer through transcriptional silencing of critical growth regulators such as tumor suppressor genes. Other chromatin modifications, such as histone deacetylation and chromatin-binding proteins, affect local chromatin structure and, in concert with DNA methylation, regulate gene transcription. The DNA methylation inhibitors azacitidine and decitabine can induce functional re-expression of aberrantly silenced genes in cancer, causing growth arrest and apoptosis in tumor cells. These agents, along with inhibitors of histone deacetylation, have shown clinical activity in the treatment of certain hematologic malignancies where gene hypermethylation occurs. This review examines alteration in DNA methylation in cancer, effects on gene expression, and implications for the use of hypomethylating agents in the treatment of cancer.

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Figure 1: Effects of DNA methylation and chromatin structure on gene transcription in normal and tumor cells.
Figure 2: DNA methylation in normal and cancer cells.
Figure 3: Metabolism of azacitidine and decitabine.
Figure 4: Hypomethylation and gene reactivation by azacitidine.

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Authors and Affiliations

  1. the Associate Director for Basic Research, Head of the Cancer Biology Program, and the Ludwig Professor of Oncology and Medicine at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Stephen B Baylin

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Correspondence to Stephen B Baylin.

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Competing interests

Dr Baylin is a consultant to OncoMethylome Sciences. Under licensing agreement between the Johns Hopkins University and this company, M.S.P. was licensed to OncoMethylome Sciences, and they are entitled to a share of the royalties received by the University from sales of the licensed technology. Also Dr Baylin is a consultant for and received research support from BioNumerik Pharmaceuticals, Inc.

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Baylin, S. DNA methylation and gene silencing in cancer. Nat Rev Clin Oncol 2 (Suppl 1), S4–S11 (2005). https://doi.org/10.1038/ncponc0354

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