DNA methylation in cancer: a gene silencing mechanism and the clinical potential of its biomarkers

Tohoku J Exp Med. 2013 Mar;229(3):173-85. doi: 10.1620/tjem.229.173.


Initiation and progression of human cancer not only depends on genetic alterations but also on epigenetic changes such as DNA methylation and histone modifications. Aberrant DNA hypermethylation in the promoter regions of genes is the most well-defined epigenetic change in tumors and is associated with inappropriate gene silencing. This feature can be utilized to search for tumor-specific DNA methylation biomarkers and to examine candidate DNA biomarkers for clinical use. DNA methylation biomarker is defined as a molecular target that undergoes DNA methylation changes in carcinogenesis. Such a biomarker is useful for early detection of cancer, predicting and/or monitoring the therapeutic response, and detection of recurrent cancer. In this review, we describe the mechanism that establishes and maintains DNA methylation patterns as well as the mechanism of aberrant gene silencing in cancer, and then we introduce methods to isolate the DNA methylation biomarkers. We also summarize the current status of clinical implementation for some of the most widely studied and well-validated DNA methylation biomarkers, including tissue factor pathway inhibitor 2 (TFPI2), septin 9 (SEPT9), glutathione S-transferase pi 1 (GSTP1), and O(6)-methylguanine-DNA methyltransferase (MGMT), and assess the clinical potential of these biomarkers for risk assessment, early diagnosis, prognosis, treatment, and the prevention of cancer. Finally we describe the possible involvement of 5-hydroxymethylcytosine in cancer; this is a recently discovered 5-methylcytosine oxidation derivative and might have a diagnostic potential in certain cancers. Abnormal DNA methylations are leading candidates for the development of specific markers for cancer diagnosis and therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Base Sequence
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • DNA Methylation / genetics*
  • Gene Silencing*
  • Humans
  • Molecular Sequence Data
  • Neoplasms / genetics*
  • Promoter Regions, Genetic / genetics


  • Biomarkers, Tumor