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Genes 2018, 9(7), 365; https://doi.org/10.3390/genes9070365

Cellular Genomic Sites of Hepatitis B Virus DNA Integration

1
Centenary Institute, University of Sydney, Sydney NSW 2050, Australia
2
South Western Sydney Clinical School, University of New South Wales, Liverpool NSW 2170, Australia
3
Gastroenterology, Liverpool Hospital, Liverpool NSW 2170, Australia
4
Department of Infectious Diseases, Molecular Virology, Heidelberg Hospital University, D-69120 Heidelberg, Germany
5
German Center for Infection Research (DZIF), Partner Site Heidelberg, D-69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Received: 26 June 2018 / Revised: 12 July 2018 / Accepted: 12 July 2018 / Published: 20 July 2018
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Abstract

Infection with the Hepatitis B Virus (HBV) is one of the strongest risk-factors for liver cancer (hepatocellular carcinoma, HCC). One of the reported drivers of HCC is the integration of HBV DNA into the host cell genome, which may induce pro-carcinogenic pathways. These reported pathways include: induction of chromosomal instability; generation of insertional mutagenesis in key cancer-associated genes; transcription of downstream cancer-associated cellular genes; and/or formation of a persistent source of viral protein expression (particularly HBV surface and X proteins). The contribution of each of these specific mechanisms towards carcinogenesis is currently unclear. Here, we review the current knowledge of specific sites of HBV DNA integration into the host genome, which sheds light on these mechanisms. We give an overview of previously-used methods to detect HBV DNA integration and the enrichment of integration events in specific functional and structural cellular genomic sites. Finally, we posit a theoretical model of HBV DNA integration during disease progression and highlight open questions in the field. View Full-Text
Keywords: Hepatitis B Virus; hepatocellular carcinoma (HCC); next generation sequencing; inverse nested PCR; chromosomal instability; insertional mutagenesis; non-homologous end joining; cancer evolution; clonal expansion; viral persistence Hepatitis B Virus; hepatocellular carcinoma (HCC); next generation sequencing; inverse nested PCR; chromosomal instability; insertional mutagenesis; non-homologous end joining; cancer evolution; clonal expansion; viral persistence
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Budzinska, M.A.; Shackel, N.A.; Urban, S.; Tu, T. Cellular Genomic Sites of Hepatitis B Virus DNA Integration. Genes 2018, 9, 365.

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