Gastroenterologia Japonica

, Volume 25, Supplement 2, pp 43–48 | Cite as

Integration of hepatitis virus DNA near c-myc in woodchuck hepatocellular carcinoma

  • Tsuey-ying Hsu
  • Geneviéve Fourel
  • Jeanne Etiemble
  • Pierre Tiollais
  • Marie-Annick Buendia
Proceeding of the International Symposium on Biology of Hepatitis B Virus and Non-A Non-B Hepatitis Virus


A total of 33 hepatocellular carcinomas, induced in woodchucks by chronic infection with woodchuck hepatitis virus (WHV), a virus closely related to the human hepatitis B virus, were analyzed for the state of viral DNA, the expression of viral genes and of different cellular proto-oncogenes. Low levels of viral replication and presence of integrated viral forms including sequences of the enhancer element, appeared as a general rule in these tumors. Enhanced expression of one or more of the nuclear protooncogenes: c-myc, N-myc, c-fos, c-jun and jun-B was frequently observed. In two hepatomas, elevated expression and allelic alterations of c-myc were subsequent to integration of WHV DNA near the c-myc coding domain. The viral strategy for insertional activation of c-myc in these tumors appeared basically identical to that of mammalian retroviruses in T-cell lymphomas of mice and rats. Whether insertional mutagenesis of different oncogenes may be more generally linked to liver oncogenesis induced by WHV and hepatitis B viruses remains to be determined.

Key words

c-myc proto-oncogene hepatitis B virus hepatocellular carcinoma insertional mutagenesis woodchuck 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Beasley RP, Hwang LY: Epidemiology of hepatocellular carcinoma. In: Vyas GN, Dienstag JI, Hoofnagle JH, eds. Viral hepatitis and liver disease. Grune and Stratton, New York. 1984;209–224Google Scholar
  2. 2.
    Brechot C, Pourcel C, Hadchouel M, et al: State of hepatitis B virus DNA in liver diseases. Hepatology 1982;2:27S-34SGoogle Scholar
  3. 3.
    Chen DS, Hoyer BH, Nelson J, et al: Detection and properties of hepatitis BvirusDNAin liver tissues from patients with hepatocellular carcinoma. Hepatology 1982;2:42S-45SGoogle Scholar
  4. 4.
    Hino O, Kitagawa T, Koike K, et al: Detection of hepatitis B virus DNA in hepatocellular carcinomas in Japan. Hepatology 1984;4:90–95PubMedCrossRefGoogle Scholar
  5. 5.
    Popper H, Roth L, Purcell R, et al: Hepatocarcinogenicity of the woodchuck hepatitis virus. Proc Natl Acad Sci USA 1987;84:866–870PubMedCrossRefGoogle Scholar
  6. 6.
    Maniatis T, Fritsch EF, Sambrook J: Molecular cloning: A laboratory manual. Cold Spring Harbor, Cold Spring Harbor Laboratory, New York. 1982Google Scholar
  7. 7.
    Möröy T, Marchio A, Etiemble J, et al: Rearrangement and enhanced expression of c-myc in hepatocellular carcinoma of hepatitis virus infected woodchucks. Nature 1986;324:276–279PubMedCrossRefGoogle Scholar
  8. 8.
    Etiemble J, Möröy T, Jacquemin E, et al: Fused transcripts of cmyc and a new cellular locus, hcr in a primary liver tumor. Oncogene 1989;4:51–57PubMedGoogle Scholar
  9. 9.
    Hsu TY, Möröy T, Etiemble J, et al: Activation of c-myc by woodchuck hepatitis virus insertion in hepatocellular carcinoma. Cell 1988;55:627–635PubMedCrossRefGoogle Scholar
  10. 10.
    Bishop JM: The molecular genetics of cancer. Science 1987;235: 305–311PubMedCrossRefGoogle Scholar
  11. 11.
    Corcoran LM, Adams JM, Dunn AR, et al: Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion. Cell 1984;37:113–122PubMedCrossRefGoogle Scholar
  12. 12.
    Leder A, Pattengale PK, Kuo A, et al: Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell 1986;45:485–495PubMedCrossRefGoogle Scholar
  13. 13.
    Rogler C, Sherman M, Su C, et al: Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma. Science 1985;230:319–322PubMedCrossRefGoogle Scholar
  14. 14.
    Hino O, Shows T, Rogler C: Hepatitis B virus integration site in hepatocellular carcinoma at chromosome 17;18 translocation. Proc Natl Acad Sci USA 1986;83:8338–8342PubMedCrossRefGoogle Scholar
  15. 15.
    Dejean A, Bougueleret L, Grzeschik KH, et al: Hepatitis B virus DNA integration in a sequence homologous to c-erb-A and steroid receptor genes in a hepatocellular carcinoma. Nature 1986;322:70–72PubMedCrossRefGoogle Scholar
  16. 16.
    Ochiya T, Jujiyama A, Fukushige S, et al: Molecular cloning of an oncogene from a human hepatocellular carcinoma. Proc Natl Acad Sci USA 1986;83:4993–4997PubMedCrossRefGoogle Scholar
  17. 17.
    Nagaya T, Nakamura T, Tokino T, et al: the mode of hepatitis B virus DNA integration in chromosomes of human hepatocellular carcinoma. 1987; 1:773–782Google Scholar

Copyright information

© The Japanese Society of Gastroenlerology 1990

Authors and Affiliations

  • Tsuey-ying Hsu
    • 1
  • Geneviéve Fourel
    • 1
  • Jeanne Etiemble
    • 1
  • Pierre Tiollais
    • 1
  • Marie-Annick Buendia
    • 1
  1. 1.Unité de Recombinaison et Expression Génétique (INSERM U.163, CNRS UA.271)Institut PasteurParis Cédex 15France

Personalised recommendations