DNA methylation changes in normal liver tissues and hepatocellular carcinoma with different viral infection

Exp Mol Pathol. 2010 Apr;88(2):287-92. doi: 10.1016/j.yexmp.2010.01.002. Epub 2010 Jan 14.

Abstract

Hepatocellular carcinoma (HCC) is known to be associated with both HBV and HCV. While epigenetic changes have been previously reported to be associated with hepatocellular carcinoma (HCC), whether the epigenetic profile of HBC associated HCC differs from that of HCV-associated HCC is unclear. We analyzed DNA methylation of ten genes (APC, CCND2, CDKN2A, GSTP1, HOXA9, RARB, RASSF1, RUNX, SFRP1, and TWIST1) using MethyLight assays on 65 archived liver tissue blocks. Three genes (APC, CCND2, and GSTP1) were frequently methylated in normal liver tissues. Five genes (APC, CDKN2A, HOXA9, RASSF1, and RUNX) were significantly more frequently methylated in malignant liver tissues than normal liver tissues. Among HCC cases, HOXA9, RASSF1 and SFRP1 were methylated more frequently in HBV-positive HCC cases, while CDKN2A were significantly more frequently methylated in HCV-positive HCC cases. Our data support the hypothesis that HCC resulting from different viral etiologies is associated with different epigenetic changes.

MeSH terms

  • Adult
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Core Binding Factor alpha Subunits / genetics
  • DNA Methylation / physiology*
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / isolation & purification
  • Female
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic
  • Genes, APC
  • Genes, p16
  • Hepatitis B / complications*
  • Hepatitis C / complications*
  • Homeodomain Proteins / genetics
  • Humans
  • Liver / metabolism*
  • Liver Neoplasms / complications
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Racial Groups
  • Tumor Suppressor Proteins / genetics

Substances

  • Core Binding Factor alpha Subunits
  • DNA, Neoplasm
  • Homeodomain Proteins
  • RASSF1 protein, human
  • Tumor Suppressor Proteins
  • homeobox protein HOXA9