title: 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: 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.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Hong
authors.initials: H
authors.lastname: Kim
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Jee
authors.forename: Ho-Suk
authors.initials: HS
authors.lastname: Mun
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Yoon-Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Hyun
authors.forename: Eung-Soo
authors.initials: ES
authors.lastname: Hwang
authors.forename: Chang-Yong
authors.initials: CY
authors.lastname: Cha
authors.forename: Yoon-Hoh
authors.initials: YH
authors.lastname: Kook
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Kim
mesh_terms: 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
chemical_list: D006513:Hepatitis B e Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein