Chapter 41 - Mutations of the core gene sequence of HCV from patients with hepatocellular carcinoma in China

Abstract

The association between hepatocellular carcinoma (HCC) and the genomic characteristics of the hepatitis C virus (HCV) isolated from China is investigated in this chapter. The data reveal 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 mutations in the clustering variable region (CVR) is higher. 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 greater in liver tissues than in sera from HCC patients. An amino acid alteration from glycine (Gly) to serine (Ser) at core codon 45 in the CVR was dominant in noncancerous portions rather than 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.