DNA methylation changes in normal liver tissues and hepatocellular carcinoma with different viral infection.
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.
Feng
Qinghua
Q
Department of Pathology, School of Medicine, University of Washington, Seattle, Washington 98109, USA. qf@u.washington.edu
Stern
Joshua E
JE
Hawes
Stephen E
SE
Lu
Hiep
H
Jiang
Mingjun
M
Kiviat
Nancy B
NB
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050657:Core Binding Factor alpha Subunits / Q000235:genetics; D019175:DNA Methylation / Q000502:physiology*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D019942:Genes, p16; D006509:Hepatitis B / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044469:Racial Groups; D025521:Tumor Suppressor Proteins / Q000235:genetics
D050657:Core Binding Factor alpha Subunits; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C097899:homeobox protein HOXA9