COOH-terminal deletion of HBx gene is a frequent event in HBV-associated hepatocellular carcinoma.
OBJECTIVE
To investigate the hepatitis B virus (HBV)x gene (HBx) state in the tissues of HBV-related hepatocellular carcinoma (HCC) in Chinese patients and whether there were particular HBx mutations.


METHODS
HBx gene was amplified and direct sequencing was used in genomic DNA samples from 20 HCC and corresponding non-cancerous liver tissues from HBsAg-positive patients. HBV DNA integration and HBx deleted mutation were validated in 45 HCC patients at different stages by Southern blot analysis and polymerase chain reaction methods.


RESULTS
The frequencies of HBx point mutations were significantly lower in HCC than their corresponding non-cancerous liver tissues (11/19 vs 18/19, P=0.019). In contrast, deletions in HBx gene were significantly higher in HCC than their non-cancerous liver tissues (16/19 vs 4/19, P<0.001). The deletion of HBx COOH-terminal was detected in 14 HCC tissues. A specific integration of HBx at 17p13 locus was also found in 8 of 16 HCC, and all of them also exhibited full-length HBx deletions. Integrated or integrated coexistence with replicated pattern was obtained in 45.5% (20/45)-56.8% (25/45) tumors and 40.9% (18/45)-52.3% (23/45) non-tumor tissues.


CONCLUSIONS
HBx deletion, especially the COOH-terminal deletion of HBx is a frequent event in HBV-associated HCC tissues in China. HBV integration had also taken place in partial HCC tissues. This supporting the hypothesis that deletion and probably integrated forms of the HBx gene may be implicated in liver carcinogenesis.
Liu
Xiao-Hong
XH
Department of Pathology, Changhai Hospital, Second Military Medical University, 174 Changhai Road, Shanghai 200433, China.
Lin
Jing
J
Zhang
Shu-Hui
SH
Zhang
Shun-Min
SM
Feitelson
Mark-A
MA
Gao
Heng-Jun
HJ
Zhu
Ming-Hua
MH
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics / Q000821:virology*; D016022:Case-Control Studies; D002681:China; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics*
D004273:DNA, Neoplasm; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein