Mutations of the core gene sequence of hepatitis C virus isolated from liver tissues with hepatocellular carcinoma

Abstract Our preliminary study indicated the presence of a clustering variable region (CVR) in the hepatitis C virus (HCV) core gene sequence in patients with hepatocellular carcinoma (HCC). To compare the sequence divergences of the core gene isolated from cancerous and noncancerous liver tissues in patients with HCC along with those from serum samples in patients with chronic hepatitis (CH), liver cirrhosis (LC), and HCC, we determined nucleotide and deduced amino acid (AA) sequences in a part of the core gene that included the CVR. The sequence diversity in the core gene increased with the progression from CH to LC or HCC and the number of nucleotide substitutions giving rise to changes in AA residues in the CVR was significantly greater in liver tissues than in sera from HCC patients. Moreover, the number of AA 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 AA 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 AA sequence changes in the HCV core gene from liver tissue, might be related to hepatocarcinogenesis.