title: A pre-S gene chip to detect pre-S deletions in hepatitis B virus large surface antigen as a predictive marker for hepatoma risk in chronic hepatitis B virus carriers.
abstract: BACKGROUND
  Chronic hepatitis B virus (HBV) infection is an important cause of hepatocellular carcinoma (HCC) worldwide. The pre-S1 and -S2 mutant large HBV surface antigen (LHBS), in which the pre-S1 and -S2 regions of the LHBS gene are partially deleted, are highly associated with HBV-related HCC.
  
  
  METHODS
  The pre-S region of the LHBS gene in two hundred and one HBV-positive serum samples was PCR-amplified and sequenced. A pre-S oligonucleotide gene chip was developed to efficiently detect pre-S deletions in chronic HBV carriers. Twenty serum samples from chronic HBV carriers were analyzed using the chip.
  
  
  RESULTS
  The pre-S deletion rates were relatively low (7%) in the sera of patients with acute HBV infection. They gradually increased in periods of persistent HBV infection: pre-S mutation rates were 37% in chronic HBV carriers, and as high as 60% in HCC patients. The Pre-S Gene Chip offers a highly sensitive and specific method for pre-S deletion detection and is less expensive and more efficient (turnaround time 3 days) than DNA sequencing analysis.
  
  
  CONCLUSIONS
  The pre-S1/2 mutants may emerge during the long-term persistence of the HBV genome in carriers and facilitate HCC development. Combined detection of pre-S mutations, other markers of HBV replication, and viral titers, offers a reliable predictive method for HCC risks in chronic HBV carriers.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan, Republic of China. jin2348257@hotmail.com
authors.forename: Fan-Ching
authors.initials: FC
authors.lastname: Shen
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Wu
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Yao
authors.forename: Kung-Chia
authors.initials: KC
authors.lastname: Young
authors.forename: Tsung-Chuan
authors.initials: TC
authors.lastname: Chang
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Hsieh
authors.forename: Han-Ni
authors.initials: HN
authors.lastname: Tsai
authors.forename: Wenya
authors.initials: W
authors.lastname: Huang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology; D004252:DNA Mutational Analysis / Q000295:instrumentation*; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D006511:Hepatitis B Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000097:blood / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012306:Risk; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D006511:Hepatitis B Antigens; C096362:L protein, hepatitis B virus; D014759:Viral Envelope Proteins