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Expression of mutated hepatitis B virus X genes in human hepatocellular carcinomas
Author(s) -
Poussin Karine,
Dienes Hans,
Sirma Hüseyin,
Urban Stefan,
Beaugrand Michel,
Franco Dominique,
Schirmacher Peter,
Bréchot Christian,
Paterlini Bréchot Patrizia
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990209)80:4<497::aid-ijc3>3.0.co;2-8
Subject(s) - hepatitis b virus , biology , hbsag , frameshift mutation , carcinogenesis , gene , virology , reverse transcriptase , rna , hepatocellular carcinoma , microbiology and biotechnology , virus , antigen , mutation , exon , cancer research , immunology , genetics
To explore the role of hepatitis B virus (HBV) X protein in liver carcinogenesis, independently from its role in viral replication, we have analyzed X gene structure and expression in tumorous and non‐tumorous tissues obtained from 9 hepatitis B surface antigen (HBsAg)‐negative, HBV DNA‐positive patients. HBV replication was undetectable in tumorous tissues. HBV X gene was truncated at its 3′ end in 5 of 9 tumorous tissues and 1 of 8 non‐tumorous livers. Sequence analysis performed on uninterrupted X genes from 3 tumors and 3 surrounding non‐tumorous tissues showed a high rate of mutations, selectively in the tumorous livers. In 1 of the 3 tumors, a frameshift mutation induced a new stop at codon 129. HBV RNAs were tested by reverse transcriptase‐polymerase chain reaction (RT‐PCR) with surface (S), core (C) and X specific primers. X, but not S and C, RNA expression was found in 6 of 8 tumors and in 6 of 7 non‐tumorous tissues. This finding was consistent with immunohistochemical detection of X, but not S and C, antigens in all tumors also expressing X RNA. Our results provide evidence for selective expression of HBV X, but not S and C, RNA and protein in the tumorous and non‐tumorous tissue of HBsAg‐negative, HBV DNA‐positive patients. It also shows that the structure of the X gene is modified (interrupted or highly mutated) in the majority of tumorous livers. Taken together, our findings are consistent with a potential role of mutated X proteins in HBV‐related liver oncogenesis. Int. J. Cancer 80:497–505, 1999. © 1999 Wiley‐Liss, Inc.