Mutations of the core gene sequence of HCV from patients with hepatocellular carcinoma in China and Japan

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Firstly, we investigated the association between hepatocellular carcinoma(HCC)and the genomic characteristics of the hepatitis C virus(HCV)isolated from residents of the inshore region of the Yangtze River. That area of China has one of the highest incidences of HCC.Our data revealed that nucleotide substitutions are unevenly scattered along the HCV genome, with a cluster of missense mutations in the region encoding the second hydrophilic domain of the core protein, and that the number of these mutations in the clustering variable region(CVR)is significantly higher in isolates from HCC patients than in those from individuals with chronic hepatitis. Secondly, we determined the sequence divergence of the CVR in HCV isolates from cancerous and noncancerous liver tissues in Japanese patients with HCC.The number of nucleotide substitutions giving rise to changes in amino acid residues in the CVR was significantly greater in liver tissues than in sera from HCC patients. The number of amino acid residues in the CVR that differed from the representative clone from cancerous liver portions was significantly higher than the number differing from noncancerous portions in each patient. An amino acid alteration from Gly to Ser at core codon 45 in the CVR was dominant in noncancerous portions rather than in cancerous portions and sera from HCC patients. These findings suggest that a large number of mutations, including biologically important amino acid sequence changes in the HCV core gene from liver tissue, might be related to hepatocarcinogenesis.