The effects of hepatitis B virus integration into the genomes of hepatocellular

StephenW

http://genome.cshlp.org/content/early/2012/01/20/gr.133926.111.abstract%20.
The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients                                 

• Zhaoshi Jiang1,
• Suchit Jhunjhunwala1,
• Jinfeng Liu1,
• Peter M. Haverty2,
• Michael I. Kennemer3,
• Yinghui Guan4,
• William Lee5,
• Paolo Carnevali3,
• Jeremy Stinson6,
• Stephanie Johnson7,
• Jingyu Diao8,
• Stacy Yeung6,
• Adrian Jubb7,
• Weilan Ye6,
• Thomas D. Wu5,
• Sharookh B. Kapadia8,
• Frederic J. de Sauvage6,
• Robert C. Gentleman5,
• Howard M. Stern7,
• Somasekar Seshagiri6,
• Krishna P. Pant3,
• Zora Modrusan6,
• Dennis G Ballinger3 and
• Zemin Zhang5,9
  

- Author Affiliations

                  

• 1 Department of Bioinformatics and Computational Biology, Genentech Inc;
• 2 .Department of Bioinformatics and Computational Biology, Genentech Inc.;
• 3 Complete Genomics Inc.;
• 4 Department of Molecular Biology, Genentech Inc.,;
• 5 Department of Bioinformatics and Computational Biology, Genentech Inc.;
• 6 Department of Molecular Biology, Genentech Inc.;
• 7 Department of Pathology, Genentech Inc.;
• 8 Department of Microbial Pathogenesis, Genentech Inc.
  

                  

• ↵*  Corresponding author; email: [email protected]
  

               
Abstract                  

Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC). HBV integration into the host genome has been reported but its scale, impact and contribution to HCC development is not clear. Here, we sequenced the tumor                     and non-tumor genomes (>80X coverage) and transcriptomes of four HCC patients and identified 255 HBV integration sites. Increased sequencing to 240X coverage revealed a proportionally higher number of integration sites. Clonal expansion of HBV-integrated        hepatocytes was found specifically in tumor samples. We observe a diverse collection of genomic perturbations near viral integration sites, including direct gene disruption, viral promoter-driven human transcription, viral-human transcript fusion and DNA copy number alteration. Thus, we report the most comprehensive characterization of HBV integration in hepatocellular carcinoma patients. Such widespread random viral integration will likely increase carcinogenic opportunities in HBV-infected individuals.                  

               
               

• Received October 25, 2011.
• Accepted January 19, 2012.
  

               

• Copyright © 2012, Cold Spring Harbor Laboratory Press
  

                                 

This manuscript is Open Access.

               

StephenW

乙肝病毒整合到肝癌患者的基因组的影响

    赵氏江1
    suchit Jhunjhunwala1
    金丰Liu1
    彼得M Haverty2，
    迈克尔一Kennemer3，
    映辉Guan4
    威廉Lee5
    保罗Carnevali3
    杰里米Stinson6
    斯蒂芬妮Johnson7
    靖宇Diao8
    斯泰西Yeung6
    阿德里安Jubb7
    蔚蓝Ye6
    托马斯四Wu5，
    sharookh二Kapadia8，
    弗雷德里克J. DE Sauvage6，
    罗伯特C. Gentleman5，
    霍华德研究Stern7，
    somasekar Seshagiri6
    克里希纳体育Pant3，
    佐拉Modrusan6
    丹尼斯ĞBallinger3和
    江泽民Zhang5，9

- 作者背景

    1生物信息学和计算生物学，基因泰克公司;
    2，生物信息学和计算生物学，Genentech公司;
    3完整的基因组学公司;
    4分子生物学系，Genentech公司;
    生物信息学和计算生物学，Genentech公司的5部;
    6分子生物学系，Genentech公司;
    7部病理学，Genentech公司;
    8部微生物的发病机制，Genentech公司

    ↵*通讯作者;电子邮件：zhang.zemin @ gene.com

抽象

B型肝炎病毒（HBV）感染是肝细胞癌（HCC）的主要危险因素。 HBV整合到宿主基因组已被报道，但其规模，影响和肝癌发展的贡献是不明确的。在这里，我们肿瘤和非肿瘤基因组测序（80X报道）和4个肝癌患者转录，并确定了255乙型肝炎病毒整合位点。增加测序240X报道透露的整合位点的人数比例较高。专门在肿瘤样本中发现HBV集成肝细胞的克隆扩增。我们观察不同的病毒整合位点附近的基因组的扰动，包括直接的基因破坏，病毒启动子驱动的人类转录，转录病毒人类融合和DNA拷贝数改变的集合。因此，我们报告的肝癌患者HBV整合最全面的表征。如此广泛的随机病毒整合的HBV感染者可能会增加致癌的机会。

    收到2011年10月25日。
    接受，2012年1月19日。