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Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma

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.

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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

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