In:
International Journal of Cancer, Wiley, Vol. 121, No. 6 ( 2007-09-15), p. 1257-1264
Abstract:
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. © 2007 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0020-7136
,
1097-0215
Language:
English
Publisher:
Wiley
Publication Date:
2007
detail.hit.zdb_id:
218257-9
detail.hit.zdb_id:
1474822-8
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