title: Hepatitis B virus full-length genomic mutations and quasispecies in hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatitis B virus (HBV) full-length genomic mutations and quasispecies characteristics in hepatocellular carcinoma (HCC) were investigated.
  
  
  METHODS
  Hepatitis B virus DNA was extracted from the tumor and non-tumor tissues of 16 HCC patients. Overlapping DNA fragments covering the entire HBV genome were amplified and sequenced. To study HBV sequence at the quasispecies level, the preS region was amplified and clonally sequenced. HBV mutation profiles, quasispecies complexity and diversity, and phylogenetic characteristics were assessed.
  
  
  RESULTS
  Fourteen patients had full-length HBV amplification. Hot-spot mutations at HBx aa130-131 and pre-S deletions were detected in 13 (93%) and 6 (43%) patients, respectively. Deletions in the X/preC/C regions were more frequently detected in the tumor than in the non-tumor tissues (P = 0.031). Compared with the non-tumor tissues, the tumor tissues had a lower quasispecies complexity (P = 0.014 and 0.043, at the nucleotide and amino acid levels, respectively) and diversity (P = 0.048 and 0.022, at the nucleotide and amino acid levels, respectively). Phylogenetic analysis showed that HBV sequences derived from tumor and non-tumor tissues were separately clustered, suggesting the occurrence of compartmentalization, which was confirmed by the correlation coefficient testing on both the number and length of branches of viral populations (all P < 0.02).
  
  
  CONCLUSIONS
  Hepatitis B virus mutation patterns in HCC tumor tissues and non-tumor tissues were different. HBV quasispecies within the preS region were compartmentalized, and tumor tissues had a lower genome complexity and diversity. Our study suggests HBV evolution is conditioned by the differential host cellular environment in HCC tumors.
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: An-Ye
authors.initials: AY
authors.lastname: Zhang
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.affiliation: State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong SAR, China.|Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ronnie Tung-Ping
authors.initials: RT
authors.lastname: Poon
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Fung-Yu
authors.initials: FY
authors.lastname: Huang
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Wai-Kay
authors.initials: WK
authors.lastname: Seto
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: James
authors.initials: J
authors.lastname: Fung
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong SAR, China. danywong@hku.hk.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong SAR, China. danywong@hku.hk.
authors.forename: Danny Ka-Ho
authors.initials: DK
authors.lastname: Wong
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong SAR, China. mfyuen@hkucc.hku.hk.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong SAR, China. mfyuen@hkucc.hku.hk.
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000821:virology*; D006801:Humans; D008099:Liver / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009154:Mutation; D010802:Phylogeny; D012367:RNA, Viral / Q000032:analysis; D017422:Sequence Analysis, DNA
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral
keywords: full-length genome sequencing; hepatitis B virus; hepatocellular carcinoma; mutation; quasispecies