Differential DNA methylation associated with hepatitis B virus infection in hepatocellular carcinoma.

Gene inactivation through DNA hypermethylation plays a pivotal role in carcinogenesis. This study aimed to profile aberrant DNA methylation in different stages of liver disease, namely noncirrhosis, cirrhosis and hepatocellular carcinoma (HCC), and also to clarify the influence of hepatitis B virus (HBV) infection on the aberrant DNA methylation in HCCs. Promoter methylation in p14(ARF), p16(INK4a), O(6)-methylguanine-DNA methyltransferase (MGMT), glutathione S-transferase pi (GSTP1) and E-cadherin (E-Cad) genes of 58 HCCs paired with adjacent nontumorous tissues was assayed by methylation-specific PCR. HBV infection was determined using a hepatitis B virus surface antigen (HBsAg) serological assay. The frequency of p16(INK4a) promoter methylation increased from noncirrhotic, cirrhotic, to HCC tissues (noncirrhotic vs. HCC, p < 0.001), while that of GSTP1 promoter methylation increased in cirrhotic tissues compared to noncirrhotic ones (p = 0.029). The frequency of GSTP1 promoter hypermethylation is significantly higher in HCC than in nontumorous tissues (p = 0.022) from HBsAg-positive patients, but not the HBsAg-negative controls (p = 0.289). While the frequency of E-Cad promoter hypermethylation remained high in both nontumorous tissues and HCCs from HBsAg-positive patients (p = 0.438), it was lower in HCCs than in nontumorous tissues from HBsAg-negative patients (p = 0.002). In contrast, the frequency of p16(INK4a), MGMT and p14(ARF) promoter hypermethylation in HCCs was unrelated to HBsAg status. In conclusion, aberrant DNA methylation may begin at different stages of liver disease in a gene-dependent manner. Moreover, HBV infection may enhance or maintain GSTP1 and E-Cad promoter methylation and thereby affect hepatocarcinogenesis.

Su PF ，Lee TC ，Lin PJ ，Lee PH ，Jeng YM ，Chen CH ，Liang JD ，Chiou LL ，Huang GT ，Lee HS ... -  《INTERNATIONAL JOURNAL OF CANCER》

[Aberrant methylation of multiple genes and its clinical implication in hepatocellular carcinoma].

Lou C ，Yang B ，Gao YT ，Wang YJ ，Nie FH ，Yuan Q ，Zhang CL ，Du Z ... -  《-》

Promoter hypermethylation of p14 (ARF) , RB, and INK4 gene family in hepatocellular carcinoma with hepatitis B virus infection.

Zhang JC ，Gao B ，Yu ZT ，Liu XB ，Lu J ，Xie F ，Luo HJ ，Li HP ... -  《-》

Methylation framework of cell cycle gene inhibitors in cirrhosis and associated hepatocellular carcinoma.

Roncalli M ，Bianchi P ，Bruni B ，Laghi L ，Destro A ，Di Gioia S ，Gennari L ，Tommasini M ，Malesci A ，Coggi G ... -  《HEPATOLOGY》

Aberrant gene promoter methylation of E-cadherin, p16 (INK4a) , p14 (ARF) , and MGMT in Epstein-Barr virus-associated oral squamous cell carcinomas.

Burassakarn A ，Pientong C ，Sunthamala N ，Chuerduangphui J ，Vatanasapt P ，Patarapadungkit N ，Kongyingyoes B ，Ekalaksananan T ... -  《-》