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Journal of Clinical Microbiology, October 2002, p. 3625-3630, Vol. 40, No. 10
0095-1137/02/$04.00+0 DOI: 10.1128/JCM.40.10.3625-3630.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Departments of Microbiology,1 Gastroenterological Surgery,2 Clinical Molecular Medicine,3 International Center for Medical Research, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan4
Received 28 January 2002/ Returned for modification 21 March 2002/ Accepted 27 June 2002
The core protein of hepatitis C virus (HCV) has been implicated in hepatocarcinogenesis. In order to determine whether there is a correlation between mutations of the core protein and the development of hepatocellular carcinoma (HCC), the core protein-coding sequence of the viral genome of HCV subtype 1b (HCV-1b) obtained from patients with and without HCC was analyzed. We found that 12 (40.0%) of 30 HCV-1b isolates from patients with HCC but none of 29 isolates from patients without HCC had a point mutation(s) in an N-terminal region of 20 residues. Similarly, 10 (33.3%) of 30 isolates from patients with HCC had mutations in a limited region between residues 141 and 160, whereas only 2 (6.9%) of 29 isolates from patients without HCC did. The differences between the two groups were statistically significant. The mutations were found in isolates from both cancerous and adjacent noncancerous tissues of patients with HCC, suggesting that the mutations were present before the development of HCC. The other regions of the core protein of some isolates also had mutations, but no significant difference was observed between isolates from patients with HCC and those from patients without HCC. The F protein, a frameshift product that is still hypothetical for HCV-1b strains, showed more sequence diversity than the core protein among the isolates analyzed, but there were no significant differences in the mutation rates or positions between isolates from patients with HCC and isolates from patients without HCC, except for a short N-terminal sequence of
11 residues that is shared with the core protein.
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