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Integration of hepatitis B virus DNA in hepatocellular carcinoma tissue

Lin, Yue; (1991) Integration of hepatitis B virus DNA in hepatocellular carcinoma tissue. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Hepatitis B virus (HBV) infection and subsequent viral DNA integration have been suggested to play an important role in the development of human hepatocellular carcinoma (HCC). Ten HBV-related HCC samples from South Africa and China were analyzed by Southern blot hybridisation with genomic and subgenomic HBV DNA probes. Nine tumours contained integrated HBV DNA; four had a single integrant and the rest more than one. Genomic DNAs from three single-integrant- positive tumours and two samples with a simple pattern of viral DNA integration were further molecularly cloned, and integrated HBV DNA and the flanking cellular sequences of the clone LAI la were analyzed in detail by restriction mapping and DNA sequencing. Clone LAI la unfortunately contained only the upstream virus-host junction. An attempt was made to modify the polymerase chain reaction (PCR) technique to amplify the downstream virus-host sequences without success. In summary, the single HBV integrant of tumour A1 is more than 2.7 kb in length and contains all regions of HBV genome. The viral DNA integration occurs in an intron or some non-transcribed cellular sequences and one of the virus-host junctions lies at nt 1881 only 47 bp downstream of HBV DR1 (nt 1824-1834), sequences around which are known to be hotspots for integration. The feature of an in-phase stop codon, TAG, in the pre-C region of the integrated HBV DNA has also been observed, although there is no evidence for its association with HCC. Further, the single integrant contains certain cis-acting elements including the promoters for pre-S and surface and the X gene, an enhancer and the viral polyadenylation signal, which are essential for virus gene expression. Thus, cellular sequence(s) may have been placed under the control of these viral cis-acting sequences, leading to altered cellular gene expression and a step to liver oncogenesis. This supports the hypothesis that HBV may contribute to hepatocarcinogenesis through insertional mutagenesis.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Integration of hepatitis B virus DNA in hepatocellular carcinoma tissue
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10124019
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