| Literature DB >> 22267523 |
Zhaoshi Jiang1, Suchit Jhunjhunwala, Jinfeng Liu, Peter M Haverty, Michael I Kennemer, Yinghui Guan, William Lee, Paolo Carnevali, Jeremy Stinson, Stephanie Johnson, Jingyu Diao, Stacy Yeung, Adrian Jubb, Weilan Ye, Thomas D Wu, Sharookh B Kapadia, Frederic J de Sauvage, Robert C Gentleman, Howard M Stern, Somasekar Seshagiri, Krishna P Pant, Zora Modrusan, Dennis G Ballinger, Zemin Zhang.
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 nontumor genomes (>80× coverage) and transcriptomes of four HCC patients and identified 255 HBV integration sites. Increased sequencing to 240× 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.Entities:
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Year: 2012 PMID： 22267523 PMCID： PMC3317142 DOI： 10.1101/gr.133926.111
Source DB: PubMed Journal: Genome Res ISSN： 1088-9051 Impact factor: 9.043