Integrated hepatitis B virus (HBV) DNA previously cloned from a hepatocellular carcinoma genomic library derived from a Japanese patient was characterized further. Sequence analysis of restriction fragments bearing the virus-host junctions defined 3125 nucleotides of essentially un-rearranged HBV DNA of the adr subtype with the right junction mapping within the cohesive region at position 1970 and the left within the pre-core at position 1886. The right viral-host junction contains a 7 bp repeat (TGTAGGC) and a possible 2 bp inversion. The integrated HBV DNA includes the complete open reading frames for core, pre-S, S and polymerase and a 3′ truncated X gene, and lacks most of the pre-core. Integration has occurred at a mutational hot spot of the viral genome and appears to be located in a region of semi-repetitive genomic DNA 3′ to the β-globin gene cluster.
BalsanoC.,
AvantaggiatiM. L.,
NatoliG.,
DemarzioE.,
WillH.,
PerricaudetM.,
LevreroM.1991; Full-length and truncated versions of the hepatitis-B virus (HBV) X-protein (PX) transactivate the c-myc protooncogene at the transcription level. Biochemical and Biophysical Research Communications 176:985–992
FowlerM. J. F.,
ThomasH. C.,
MonjardinoJ.1986; Cloning and analysis of integrated hepatitis B virus DNA of the adr subtype derived from a human primary liver cell carcinoma. Journal of General Virology 67:771–775
HattoriM.,
HidakaS.,
SakakiY.1985; Sequence analysis of a Kpn I family member near the 3′ end of the human β-globin gene. Nucleic Acids Research 13:7813–7827
HinoO.,
OhtakeK.,
RoglerC.1989; Features of two hepatitis B virus (HBV) integrations suggest mechanisms of HBV integration. Journal of Virology 63:2638–2643
OnoY.,
OndaH.,
SasadaR.,
IgarashiK.,
SuginaY.,
NishokaK.1983; The complete nucleotide sequences of the cloned hepatis B virus DNA; subtypes adr and adw. Nucleic Acids Research 11:1747–1757
ShihC.,
BurkeK.,
ChouM.-J.,
ZeldisJ.,
YangC.-S.,
LeeC.-S.,
IsselbacherK.,
WandsJ.,
GoodmanH.1987; Tight clustering of human hepatitis B virus integration sites in hepatomas near a triple-stranded region. Journal of Virology 61:3491–3498
YaginumaK.,
KobayashiM.,
YoshidaE.,
KoikeK.1985; Hepatitis B virus integration in hepatocellular carcinoma DNA: duplication of cellular flanking sequences at the integration site. Proceedings of the National Academy of Sciences, U.S.A 82:4458–4462
YaginumaK.,
KobayashiH.,
KobayashiM.,
MorishimaT.,
MatsuyamaK.,
KoikeK.1987; Multiple integration sites of hepatitis B virus DNA in hepatocellular carcinoma and chronic active hepatitis tissues from children. Journal of Virology 61:1808–1813
ZagurskyR.J.,
BaumeiterK.,
LomaxN.,
BermanM.1985; Rapid and easy sequencing of large linear double stranded DNA and supercoiled plasmid DNA. Gene Analysis Techniques 2:89–94
ZhouY.-Z.,
SlagleB.,
DonehowerL.,
van TuinenP.,
LedbetterD.,
ButelJ.1988; Structural analysis of hepatitis B virus genomes integrated into chromosome 17p of a human hepatocellular carcinoma. Journal of Virology 62:4224–4231