Epigenetic biomarkers of promoter DNA methylation in the new era of cancer treatment

Cancer Sci. 2018 Dec;109(12):3695-3706. doi: 10.1111/cas.13812. Epub 2018 Oct 26.

Abstract

Promoter DNA methylation, which occurs on cytosine nucleotides across CpG islands, results in gene silencing and represents a major epigenetic alteration in human cancer. Methylation-specific PCR can amplify these modifications as markers in cancer cells. In the present work, we rigorously review the published literatures describing DNA methylation in the promoters of critical tumor suppressor genes; detection of promoter DNA methylation in various body fluids permits early detection of cancer cells during perioperative courses of clinical treatment. The latest whole-genome comprehensive explorations identified excellent epigenetic biomarkers that could be detected at high frequency with high specificity; these biomarkers, which are designated highly relevant methylation genes (HRMG), permit the discrimination of tumor tissues from the corresponding normal tissues; these markers are also associated with unique cancer phenotypes, including dismal prognosis. In humans, HRMG include the CDO1, GSHR, RASSF1 and SFRP1 genes, with these markers permitting discrimination depending on the organs tested. The combination of several HRMG increased the early detection of cancer and exhibited reliable surveillance potential in human body fluids. Cancer clinics using such epigenetic biomarkers are entering a new era of enhanced decision-making with the potential for improved cancer prognosis.

Keywords: CDO1; body fluid; cancer; methylation; tumor suppressor gene.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Cysteine Dioxygenase / genetics
  • DNA Methylation*
  • Epigenesis, Genetic / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Membrane Proteins / genetics
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Promoter Regions, Genetic
  • Tumor Suppressor Proteins / genetics

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RASSF1 protein, human
  • SFRP1 protein, human
  • Tumor Suppressor Proteins
  • CDO1 protein, human
  • Cysteine Dioxygenase