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.
OBJECTIVE
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.


CONCLUSIONS
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.
Kim
Hong
H
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea.
Jee
Youngmee
Y
Mun
Ho-Suk
HS
Park
Ju-Hee
JH
Yoon
Jung-Hwan
JH
Kim
Yoon-Jun
YJ
Lee
Hyo-Suk
HS
Hyun
Jin-Won
JW
Hwang
Eung-Soo
ES
Cha
Chang-Yong
CY
Kook
Yoon-Hoh
YH
Kim
Bum-Joon
BJ
D006528:Carcinoma, Hepatocellular / Q000821:virology*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D017353:Gene Deletion; D020440:Gene Duplication; D016679:Genome, Viral; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
D006513:Hepatitis B e Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein