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Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

Author

Listed:
  • Ling-Hao Zhao

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer)

  • Xiao Liu

    (BGI-Shenzhen)

  • He-Xin Yan

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer)

  • Wei-Yang Li

    (BGI-Shenzhen
    School of Bioscience and Bioengineering, South China University of Technology)

  • Xi Zeng

    (BGI-Shenzhen
    Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong)

  • Yuan Yang

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Jie Zhao

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Shi-Ping Liu

    (BGI-Shenzhen)

  • Xue-Han Zhuang

    (BGI-Shenzhen)

  • Chuan Lin

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Chen-Jie Qin

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer)

  • Yi Zhao

    (School of Bioscience and Bioengineering, South China University of Technology)

  • Ze-Ya Pan

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Gang Huang

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Hui Liu

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Jin Zhang

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Ruo-Yu Wang

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Yun Yang

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Wen Wen

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer)

  • Gui-Shuai Lv

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer)

  • Hui-Lu Zhang

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer)

  • Han Wu

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer)

  • Shuai Huang

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Ming-Da Wang

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer)

  • Liang Tang

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer)

  • Hong-Zhi Cao

    (BGI-Shenzhen)

  • Ling Wang

    (Xijing Hospital, Fourth Military Medical University)

  • Tin-Lap Lee

    (Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong)

  • Hui Jiang

    (BGI-Shenzhen)

  • Ye-Xiong Tan

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer)

  • Sheng-Xian Yuan

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Guo-Jun Hou

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Qi-Fei Tao

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Qin-Guo Xu

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Xiu-Qing Zhang

    (BGI-Shenzhen)

  • Meng-Chao Wu

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Xun Xu

    (BGI-Shenzhen)

  • Jun Wang

    (BGI-Shenzhen
    University of Copenhagen)

  • Huan-Ming Yang

    (BGI-Shenzhen)

  • Wei-Ping Zhou

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University)

  • Hong-Yang Wang

    (Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
    National Center for Liver Cancer
    State Key Laboratory of Oncogenes and Related Genes, Cancer Institute of Renji Hospital, Shanghai Jiaotong University)

Abstract

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.

Suggested Citation

  • Ling-Hao Zhao & Xiao Liu & He-Xin Yan & Wei-Yang Li & Xi Zeng & Yuan Yang & Jie Zhao & Shi-Ping Liu & Xue-Han Zhuang & Chuan Lin & Chen-Jie Qin & Yi Zhao & Ze-Ya Pan & Gang Huang & Hui Liu & Jin Zhang, 2016. "Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma," Nature Communications, Nature, vol. 7(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12992
    DOI: 10.1038/ncomms12992
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