Abstract
HEPATITIS B virus (HBV) DNA frequently integrates into the genome of human primary liver cancer cells1–4, but the significance of this integration in liver carcinogenesis is still unclear. Here we report the cloning of a single HBV integration site in a human hepatocellular carcinoma at an early stage of development, and of its germline counterpart. The normal locus was found to be transcribed into two polyadenylated messenger RNA species of 1.8 and 2.7 kilobases. We have isolated a complementary DNA clone from a normal adult human liver cDNA library which has an open reading frame with a coding capacity for a protein of 432 amino acids and relative molecular mass 48,536. The strong homology of the C-terminal half of the protein to the A-type cyclins of clam5and Drosophila6 identifies it as a human cyclin A. The cyclin A gene has several exons, and the HBV integration occurs within an intron. As cyclins are important in the control of cell division7–17, the disruption of a cylin A gene by viral insertion might contribute to tumorigenesis.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Tiollais, P., Pourcel, C. & Dejean, A. Nature 317, 489–495 (1985).
Brechot, C., Pourcel, C., Louise, A., Rain, B. & Tiollais, P. Nature 286, 533–535 (1980).
Nagaya, T. et al. Genes Dev. 1, 773–782 (1987).
Yaginuma, K. et al. J. Virol. 61, 1808–1813 (1987).
Swenson, K. I., Farrell, K. M. & Ruderman, J. V. Cell 47, 861–870 (1986).
Lehner, C. F. & O'Farrell, P. Cell 56, 957–968 (1989).
Standart, N., Minshull, J., Pines, J. & Hunt, T. Devl Biol. 124, 248–258 (1987).
Minshull, J., Blow, J. J. & Hunt, T. Cell 56, 947–956 (1989).
Meijer, L. et al. EMBO J. 8, 2275–2282 (1989).
Pines, J. & Hunt, T. EMBO J. 6, 2987–2995 (1987).
Murray, A. M. & Kirschner, M. W. Nature 339, 275–286 (1989).
Pines, J. & Hunter, T. Cell 58, 833–846 (1989).
Solomon, M., Booher, R., Kirschner, M. & Beach, D. Cell 54, 738–739 (1988).
Goebl, M. & Byers, B. Cell 54, 739–740 (1988).
Westendorf, J. M., Swenson, K. I. & Ruderman, J. V. J. Cell Biol. 108, 1431–1444 (1989).
Draetta, G. et al. Cell 56, 829–838 (1989).
Brizuela, L., Draetta, G. & Beach, D. Proc. natn. Acad. Sci. U.S.A. 86, 4362–4366 (1989).
Draetta, G. & Beach, D. Cell 54, 17–26 (1989).
Labbe, J. C. et al. EMBO J. 8, 3053–3058 (1989).
Moria, A. O., Draetta, G., Beach, D., Wang, J. Y. J. Cell 58, 193–203 (1989).
Giordano, A. et al. Cell 58, 981–990 (1989).
Kew, M. C. & Popper, H. Sem. Liver Dis. 2, 136–146 (1984).
Beasley, R. P., Hwang, L. Y. Sem. Liver Dis. 4, 113–121 (1984).
Saguma, K. et al. Hepatology 8, 1642–1646 (1984).
Hsu, T. et al. Cell 55, 627–635 (1988).
Tokino, T. et al. J. Virol. 61, 3848–3854 (1987).
Hino, O., Ohtake, K. & Rogler, C. E. J. Virol. 63, 2638–2643 (1989).
Rogler, C. E. et al. Science 230, 319–322 (1985).
Pasquinelli, C. et al. J. Virol. 62, 629–632 (1988).
Blanquet, V., Garreau, F., Chenivesse, X., Brechot, C. & Turleau, C. Hum. Genet 80, 274–276 (1988).
Dejean, A., Bougueleret, L., Grzeschik, K. H. & Tiollais, P. Nature 322, 70–72 (1986).
De the, H., Marchio, A., Tiollais, P. & Dejean, A. Nature 330, 667–670 (1987).
Morgan, D., Kaplan, J. M., Bishop, J. M. & Varmus, H. E. Cell 57, 775–786 (1989).
Shenoy, S. et al. Cell 57, 763–774 (1989).
McVey, D. et al. Nature 341, 503–507 (1989).
Buchkovich, K., Duffy, L. A. & Harlow, E. Cell 58, 1097–1105 (1989).
Chen, P. L., Scully, P., Shew, J. Y. L. & Lee, W. H. Cell 58, 1193–1198 (1989).
Decaprio, J. A. et al. Cell 58, 1085–1095 (1989).
Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wang, J., Chenivesse, X., Henglein, B. et al. Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma. Nature 343, 555–557 (1990). https://doi.org/10.1038/343555a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/343555a0
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.