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Hepatitis B virus-related insertional mutagenesis in chronic hepatitis B patients as an early drastic genetic change leading to hepatocarcinogenesis

Oncogene volume 24, pages 4340–4348 (2005)Cite this article

Abstract

Growing evidence demonstrates that hepatitis B virus (HBV) integration and resulting insertional mutagenesis play an important role in cell growth or maintenance in hepatocellular carcinomas (HCCs). To determine if HBV integration occurs and affects cellular genes at such a stage of infection, we analysed viral–host junctions in chronic hepatitis tissues without HCC using PCR amplification with primers specific to human Alu-repeat and HBV. We obtained 42 independent viral–host junctions from six patients examined and identified chromosomal locations for 20 of the 42 junctions. In six clones, each integration apparently affected a single gene. These six candidate genes included one known tumor suppressor gene, three human homologs of drosophila genes that are critical for organ development, one putative oncogene and one recently found chemokine. Our data, together with previously reported HBV integrants in HCCs, suggested preferential HBV integration into chromosome 3 (P=0.022). Our virus-tagging approach provided (a) firm evidence of HBV integration in hepatocytes at an early stage of chronic infection and (b) revealed cellular genes possibly affected by HBV integration and potentially involved in early steps of the process leading to carcinogenesis.

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Acknowledgements

We thank Ms Naoka Maruo for her technical assistance. This study was supported by Grants-in-Aid for Scientific Research, 14570495 and 16590616 (MM), from the Ministry of Education, Culture, Sports, Science and Technology of Japan, 2002–2003 and 2004–2005.

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Authors and Affiliations

  1. Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Hirokoji, Kawaramachi, Kamigyo-ku, Kyoto, 602-8566, Japan

    Masahito Minami, Yukiko Daimon, Kojiro Mori, Hidetaka Takashima, Tomoki Nakajima, Yoshito Itoh & Takeshi Okanoue

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  1. Masahito Minami
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  2. Yukiko Daimon
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Minami, M., Daimon, Y., Mori, K. et al. Hepatitis B virus-related insertional mutagenesis in chronic hepatitis B patients as an early drastic genetic change leading to hepatocarcinogenesis. Oncogene 24, 4340–4348 (2005). https://doi.org/10.1038/sj.onc.1208628

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