Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma.
Hepatitis B virus (HBV) DNA frequently integrates into the genome of human primary liver cancer cells, 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 clam and Drosophila 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 division, the disruption of a cyclin A gene by viral insertion might contribute to tumorigenesis.
Wang
J
J
INSERM U75, CHU-Necker, Paris, France.
Chenivesse
X
X
Henglein
B
B
Bréchot
C
C
D000595:Amino Acid Sequence; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000382:microbiology*; D003001:Cloning, Molecular; D016213:Cyclins; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007447:Invertebrate Hormones / Q000235:genetics; D008113:Liver Neoplasms / Q000382:microbiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D018809:Proliferating Cell Nuclear Antigen; D012689:Sequence Homology, Nucleic Acid
D016213:Cyclins; D015342:DNA Probes; D004273:DNA, Neoplasm; D004279:DNA, Viral; D007447:Invertebrate Hormones; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA