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Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene

Oncogene volume 22, pages 3911–3916 (2003)Cite this article

Abstract

Integration of Hepatitis B Virus (HBV) DNA into liver cell DNA has been well established, but its implication in liver carcinogenesis is still being debated. In particular, insertion of the viral genome into cellular genes has been viewed as a rare event. By using HBV-Alu PCR, we have now isolated, from nine hepatocellular carcinomas, nine HBV-DNA integration sites showing that the viral genome mutates key regulatory cellular genes: neurotropic tyrosin receptor kinase 2 (NTRK2) gene, IL-1R-associated kinase 2 (IRAK2) gene, p42 mitogen-activated protein kinase 1 (p42MAPK1) gene, inositol 1,4,5-triphosphate receptor type 2 (IP3R2) gene, inositol 1,4,5-triphosphate receptor (IP3R) type 1 (IP3R1) gene, alpha 2,3 sialyltransferase (ST3GAL VI or SITA) gene, thyroid hormone uncoupling protein (TRUP) gene, EMX2-like gene, and human telomerase reverse transcriptase (hTERT) gene. This result brings to 15 the total number of genes targeted by HBV in a study of 22 human liver cancers. Overall, we found that both the inositol 1,4,5-triphosphate receptor gene and the telomerase gene were targeted by HBV in two different tumors. Thus, HBV frequently targets cellular genes involved in cell signalling and some of them may be preferential targets of the viral integration.

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Acknowledgements

This work was supported by grants from INSERM (Institut National de la Santé et de la Recherche Médicale), ARC (Association pour la Recherche sur le Cancer), FRM (Fondation pour la Recherche Médicale) and LNC (Ligue Nationale contre de Cancer).

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Authors and Affiliations

  1. INSERM/Pasteur Unit 370, Necker Faculty of Medicine, Necker-Enfants Malades Hospital, Paris, 75015, France

    Patrizia Paterlini-Bréchot, Yoshiki Murakami, Mounia Chami, Devrim Gozuacik & Christian Bréchot

  2. Second Department of Surgery, School of Medicine Chiba University, Chiba, 260-8670, Japan

    Kenichi Saigo

  3. Department of Biotechniques and Medical Informatics, Necker-Enfants Malades Hospital, Paris, 75015, France

    Claude Mugnier

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  1. Patrizia Paterlini-Bréchot
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  2. Kenichi Saigo
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Correspondence to Patrizia Paterlini-Bréchot.

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Paterlini-Bréchot, P., Saigo, K., Murakami, Y. et al. Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene. Oncogene 22, 3911–3916 (2003). https://doi.org/10.1038/sj.onc.1206492

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