Characterization of Two Hepatitis B Virus Populations in a Single Korean Hepatocellular Carcinoma Patient with an HBeAg-Negative Serostatus: A Novel X-Gene-Deleted Strain with Inverted Duplication Sequences of Upstream Enhancer Site II

Abstract

OBJECTIVES: The aim of the study was to elucidate mutation patterns related to hepatocarcinogenesis in a Korean hepatocellular carcinoma (HCC) patient. METHODS: We analyzed full genome sequences of 6 hepatitis B virus (HBV) clones from an HCC patient. RESULTS: This patient harbored 2 HBV populations with genomes of different lengths (3,221 and 2,212 bp). In addition, we found 2 characteristic features not described so far in the full-genome sequence of deleted strains. First, 3 large deletion events (847, 144 and 48 bp) and a premature termination of the 182th codon of the surface antigen could lead to truncated or possibly nonfunctional forms of all HBV proteins. Second, these showed a novel mutation type not reported to date, which is a complex of an inverted duplication of 36-bp sequences containing an upstream enhancer site II (UEII), a remote insertion, and a large deletion event of the X region by homologous recombination. CONCLUSION: The fact that UEII is a binding site of liver-specific nuclear factor, which is expressed only in highly differentiated liver cells such as cancerous HepG2, strongly suggests a relationship between this novel mutation and hepatocarcinogenesis in this patient.