Detection of hepatitis B virus dna in hepatocellular carcinoma: Analysis by hybridization with subgenomic dna fragments

Authors

  • Jen-Yang Chen,

    1. Department of Medical Microbiology and Wolfson Unit of Medical Microbiology and Parasitology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    2. Departments of Surgery and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
    Current affiliation:
    1. Department of Bacteriology, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China
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  • Tim J. Harrison Ph.D.,

    Corresponding author
    1. Department of Medical Microbiology and Wolfson Unit of Medical Microbiology and Parasitology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    2. Departments of Surgery and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
    • Department of Medical Microbiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom
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  • Chue-Shue Lee,

    1. Department of Medical Microbiology and Wolfson Unit of Medical Microbiology and Parasitology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    2. Departments of Surgery and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
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  • Ding-Shinn Chen,

    1. Department of Medical Microbiology and Wolfson Unit of Medical Microbiology and Parasitology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    2. Departments of Surgery and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
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  • Arie J. Zuckerman

    1. Department of Medical Microbiology and Wolfson Unit of Medical Microbiology and Parasitology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    2. Departments of Surgery and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
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Abstract

We have previously reported an analysis of DNA extracted from 31 primary liver tumors where, in 25 cases, we found chromosomal integration of hepatitis B virus DNA sequences. We describe here an investigation of the extent of the viral genome at each integration site in 15 of the hepatitis B virus DNA-positive tumors using subgenomic fragments of the viral genome as probes. Probes were roughly equivalent to the pre-S region, the surface antigen gene, the region containing the enhancer, the x gene and the core antigen gene. We found the core antigen gene to be that most underrepresented in the tumors and speculate that, since cells which express core antigen in the infected liver may be targeted for lysis by the immune system, modifications of the integrated viral DNA which prevent core antigen expression may be selected. Conversely, the region of the genome present in the greatest number of integrations was the surface antigen gene and, because it is known that the major surface antigen promoter is active in the integrated state, we find promoter insertion an attractive hypothesis to explain oncogenesis by hepatitis B virus.

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