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Identification of human cancer-related genes by naturally occurring Hepatitis B Virus DNA tagging

Oncogene volume 20, pages 6233–6240 (2001)Cite this article

Abstract

Proviral tagging has been used in animals as a powerful tool for cancer genetics. We show that a similar approach is possible in patients with hepatocellular carcinoma (HCC) infected by Hepatitis B Virus (HBV), a human pararetrovirus which may act by insertional mutagenesis. In this work, the HBV genome is used as a probe to identify cancer-related genes. By using HBV-Alu-PCR, we obtained 21 HBV/cellular DNA junctions from 18 different patients. In six of 21, we found the HBV DNA integrated into a cellular gene: (1) Sarco/Endoplasmic Reticulum Calcium ATPase1 Gene; (2) Thyroid Hormone Receptor Associated Protein 150 alpha Gene; (3) Human Telomerase Reverse Transcriptase Gene; (4) Minichromosome Maintenance Protein (MCM)-Related Gene; (5) FR7, a new gene expressed in human liver and cancer tissues; and (6) Nuclear Matrix Protein p84 Gene. Seven junctions contained unique cellular sequences. In the remaining eight, the HBV DNA was next to repetitive sequences, five of them of LINE1 type. The cellular genes targeted by HBV are key regulators of cell proliferation and viability. Our results show that studies on HBV-related HCCs allow to identify cellular genes involved in cancer. We therefore propose this approach as a valuable tool for functional cancer genomic studies in humans.

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Acknowledgements

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

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Author notes

  1. Devrim Gozuacik, Yoshiki Murakami, Kenichi Saigo and Mounia Chami: D Gozuacik, Y Murakami, K Saigo and M Chami contributed equally to this work

Authors and Affiliations

  1. U370 INSERM, Necker Institute, Paris, 75015, France

    Devrim Gozuacik, Yoshiki Murakami, Kenichi Saigo, Mounia Chami, David Lagorce, Christian Bréchot & Patrizia Paterlini-Bréchot

  2. Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan

    Yoshiki Murakami & Takeshi Okanoue

  3. Second Department of Surgery, Chiba University, Chiba, 263-8852, Japan

    Kenichi Saigo & Tetsuro Urashima

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

    Claude Mugnier

Authors
  1. Devrim Gozuacik
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  2. Yoshiki Murakami
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Correspondence to Patrizia Paterlini-Bréchot.

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Gozuacik, D., Murakami, Y., Saigo, K. et al. Identification of human cancer-related genes by naturally occurring Hepatitis B Virus DNA tagging. Oncogene 20, 6233–6240 (2001). https://doi.org/10.1038/sj.onc.1204835

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