Interplay of genetic and epigenetic alterations in hepatocellular carcinoma

Epigenomics. 2016 Jul;8(7):993-1005. doi: 10.2217/epi-2016-0027. Epub 2016 Jul 14.

Abstract

Genetic and epigenetic alterations play prominent roles in hepatocarcinogenesis and their appearance varies depending on etiological factors, race and tumor progression. Intriguingly, distinct patterns of these genetic and epigenetic mutations are coupled not only to affect each other, but to trigger different types of tumorigenesis. The patterns and frequencies of somatic variations vary depending on the nature of the surrounding chromatin. On the other hand, epigenetic alterations often induce genomic instability prone to mutation. Therefore, genetic mutations and epigenetic alterations in hepatocellular carcinoma appear to be inseparable factors that accelerate tumorigenesis synergistically. We have summarized recent findings on genetic and epigenetic modifications, their influences on each other's alterations and putative roles in liver tumorigenesis.

Keywords: DNA methylation; epigenetic modifications; genetic mutations; hepatocellular carcinoma; signaling pathways.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Self Renewal
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Chromosomal Instability
  • DNA Methylation
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Neoplastic Stem Cells / physiology
  • Tumor Microenvironment