p16 promoter hypermethylation in human hepatocellular carcinoma with or without hepatitis virus infection.
BACKGROUND
Epigenetic alteration through methylation is one of the most important steps in carcinogenesis. However, the relation between hepatitis virus infection and epigenetic alterations is poorly understood.


METHODS
Sixteen patients without hepatitis B virus (HBV) and hepatitis C virus (HCV) and 35 patients with HBV or HCV who underwent liver resection for hepatocellular carcinoma (HCC) were studied. Mutation of p53 was detected by direct sequencing. Methylation status of p16 was evaluated in tumor and noncancerous liver tissues by methylation-specific polymerase chain reaction.


RESULTS
In HCC without HBV and HCV, p53 mutations were detected in 5 (31%) of 16 HCCs. Methylation of p16 promoter was detected in 2 (25%) of 8 moderately differentiated HCCs, 6 (75%) of 8 poorly differentiated HCCs, and none of 16 noncancerous tissue specimens. In HCC with HBV or HCV, p53 mutations were detected in 8 (23%) of 35 HCCs. Methylation of p16 promoter was detected in 2 (100%) of 2 well-differentiated HCCs, 13 (76%) of 17 moderately differentiated HCCs, 12 (75%) of 16 poorly differentiated HCCs, and 9 (26%) of 35 noncancerous liver tissue specimens.


CONCLUSIONS
Our results suggest that hepatitis viruses might induce methylation of p16 promoter in liver with chronic inflammation, before appearance of HCC.
Narimatsu
Takashi
T
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Tamori
Akihiro
A
Koh
Noritoshi
N
Kubo
Shoji
S
Hirohashi
Kazuhiro
K
Yano
Yoshihisa
Y
Arakawa
Tetsuo
T
Otani
Shuzo
S
Nishiguchi
Shuhei
S
D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D016158:Genes, p53; D006509:Hepatitis B / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic