Structural analysis of a hepatitis B virus genome integrated into chromosome 17p of a human hepatocellular carcinoma.
Hepatitis B virus (HBV) is clearly a factor in the development of hepatocellular carcinoma, but its mechanism of action remains obscure. One possibility is that the HBV integration event alters the expression of a nearby growth-regulatory cellular gene. A 9-kilobase (kb) DNA fragment containing an HBV insert plus flanking cellular sequences was cloned from a hepatoma specimen from Shanghai, People's Republic of China. Restriction mapping of the insert revealed a large inverted repeat structure consisting of both viral sequences (encompassing all of the core and pre-S regions and portions of the X and S genes) and at least 3 kb of unique cellular sequences. The virus-cell junction mapped 11 nucleotides from the DR1 region, in a position within the HBV X gene and included in the cohesive overlap region. A probe generated from 1.0 kb of the flanking cellular DNA mapped the viral insert to chromosome 17 in the region designated 17p11.2-17p12, which is near the human proto-oncogene p53. Sequence data from a portion of the flanking cellular DNA revealed a stretch of approximately 70 base pairs that showed highly significant homology with a conserved region of a number of functional mammalian DNAs, including the human autonomously replicating sequence 1 (ARS1).
Zhou
Y Z
YZ
Department of Virology and Epidemiology, Baylor College of Medicine, Houston, Texas 77030.
Slagle
B L
BL
Donehower
L A
LA
vanTuinen
P
P
Ledbetter
D H
DH
Butel
J S
JS
D001483:Base Sequence; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000032:analysis / Q000235:genetics / Q000382:microbiology*; D002681:China; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D015342:DNA Probes; D004279:DNA, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D008113:Liver Neoplasms / Q000032:analysis / Q000235:genetics / Q000382:microbiology*; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas
D015342:DNA Probes; D004279:DNA, Viral; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas