Melanoma Epigenetics: Novel Mechanisms, Markers, and Medicines

Lab Invest. 2014 Aug;94(8):822-38. doi: 10.1038/labinvest.2014.87. Epub 2014 Jun 30.

Abstract

The incidence and mortality rates of cutaneous melanoma continue to increase worldwide, despite the deployment of targeted therapies. Recently, there has been rapid growth and development in our understanding of epigenetic mechanisms and their role in cancer pathobiology. Epigenetics--defined as the processes resulting in heritable changes in gene expression beyond those caused by alterations in the DNA sequence--likely contain the information that encodes for such phenotypic variation between individuals with identical genotypes. By altering the structure of chromatin through covalent modification of DNA bases or histone proteins, or by regulating mRNA translation through non-coding RNAs, the epigenome ultimately determines which genes are expressed and which are kept silent. While our understanding of epigenetic mechanisms is growing at a rapid pace, the field of melanoma epigenomics still remains in its infancy. In this Pathology in Focus, we will briefly review the basics of epigenetics to contextualize and critically examine the existing literature using melanoma as a cancer paradigm. Our understanding of how dysregulated DNA methylation and DNA demethylation/hydroxymethylation, histone modification, and non-coding RNAs affect cancer pathogenesis and melanoma virulence, in particular, provides us with an ever-expanding repertoire of potential diagnostic biomarkers, therapeutic targets, and novel pathogenic mechanisms. The evidence reviewed herein indicates the critical role of epigenetic mechanisms in melanoma pathobiology and provides evidence for future targets in the development of next-generation biomarkers and therapeutics.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation / drug effects
  • DNA, Neoplasm / metabolism
  • Epigenesis, Genetic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histones / metabolism
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / metabolism
  • MicroRNAs / metabolism
  • Models, Biological*
  • Molecular Targeted Therapy*
  • Neoplasm Proteins / agonists
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism
  • Protein Processing, Post-Translational / drug effects
  • RNA Interference / drug effects
  • RNA, Neoplasm / metabolism
  • RNA, Untranslated / metabolism
  • Skin / drug effects*
  • Skin / metabolism
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism

Substances

  • Antineoplastic Agents
  • Biomarkers
  • DNA, Neoplasm
  • Histone Deacetylase Inhibitors
  • Histones
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • RNA, Untranslated
  • DNA (Cytosine-5-)-Methyltransferases