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

被引：230

作者：

Jiang, Zhaoshi ^{[1
]}

Jhunjhunwala, Suchit ^{[1
]}

Liu, Jinfeng ^{[1
]}

Haverty, Peter M. ^{[1
]}

Kennemer, Michael I. ^{[2
]}

Guan, Yinghui ^{[3
]}

Lee, William ^{[1
]}

Carnevali, Paolo ^{[2
]}

Stinson, Jeremy ^{[3
]}

Johnson, Stephanie ^{[4
]}

Diao, Jingyu ^{[5
]}

Yeung, Stacy ^{[3
]}

Jubb, Adrian ^{[4
]}

Ye, Weilan ^{[3
]}

Wu, Thomas D. ^{[1
]}

Kapadia, Sharookh B. ^{[5
]}

de Sauvage, Frederic J. ^{[3
]}

Gentleman, Robert C. ^{[1
]}

Stern, Howard M. ^{[4
]}

Seshagiri, Somasekar ^{[3
]}

Pant, Krishna P. ^{[2
]}

Modrusan, Zora ^{[3
]}

Ballinger, Dennis G. ^{[2
]}

Zhang, Zemin ^{[1
]}

机构：

[1] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA

[2] Complete Genom Inc, Mountain View, CA 94043 USA

[3] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA

[4] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA

[5] Genentech Inc, Dept Microbial Pathogenesis, San Francisco, CA 94080 USA

来源：

GENOME RESEARCH | 2012年 / 22卷 / 04期

关键词：

CANCER; DNA; MUTATIONS; COMPLEX; GENES; AXIN1; MLL3;

D O I：

10.1101/gr.133926.111

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 nontumor 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.

引用

页码：593 / 601

页数：9

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