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J Med Virol 1998 Sep;56(1):18-24
HBV core promoter mutations prevail in patients with hepatocellular
carcinoma from Guangxi, China.
Fang ZL, Ling R, Wang SS, Nong J, Huang CS, Harrison TJ
University Department of Medicine, Royal Free Hospital School of Medicine,
London, United Kingdom.
The development of primary liver cancer frequently is associated with persistent
HBV infection, and tumours may arise in individuals who are anti-HBe positive.
However, it is unlear whether viruses with an HBeAg-negative phenotype are associated
with tumour development or are selected, during seroconversion, after chromosomal
integration of wild-type viral DNA. In order to investigate the temporal evolution
of the HBV genome in such individuals, the polymerase chain reaction was used
to amplify HBV DNA from tumour tissue and serum of 14 patients from Guangxi,
China with hepatocellular carcinoma. Comparison of nucleotide and amino acid
sequences of the precore and proximal core region of HBV from the two sites
in each patient produced evidence of divergence following integration in the
tumour, but in most cases, HBeAg-negativity could not be explained by precore
mutations. Sequences from the core promoter region were therefore examined and
mutations were found in the majority, which are believed to upregulate transcription
of the core (and pregenomic) RNA but to downregulate precore mRNA. To determine
whether this finding merely reflected sequence variation among geographical
isolates of HBV, the same region of HBV DNA from asymptomatic controls was sequenced
and these mutations were found to be rare. We hypothesise that HBV with the
core promoter mutations replicates at higher levels than the wild type, with
the consequence that more integrations occur into the hepatocyte chromosomes
during the early stages of infection. These hepatocytes may expand clonally
and be targets for further mutagenic events leading to tumour development.
PMID: 9700628, UI: 98365985
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