RT Journal
A1 Jiang, Zhaoshi
A1 Jhunjhunwala, Suchit
A1 Liu, Jinfeng
A1 Haverty, Peter M.
A1 Kennemer, Michael I.
A1 Guan, Yinghui
A1 Lee, William
A1 Carnevali, Paolo
A1 Stinson, Jeremy
A1 Johnson, Stephanie
A1 Diao, Jingyu
A1 Yeung, Stacy
A1 Jubb, Adrian
A1 Ye, Weilan
A1 Wu, Thomas D.
A1 Kapadia, Sharookh B.
A1 de Sauvage, Frederic J.
A1 Gentleman, Robert C.
A1 Stern, Howard M.
A1 Seshagiri, Somasekar
A1 Pant, Krishna P.
A1 Modrusan, Zora
A1 Ballinger, Dennis G.
A1 Zhang, Zemin
T1 The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients
JF Genome Research 
JO Genome Research 
YR 2012 
FD April 01 
VO 22 
IS 4 
SP 593 
OP 601 
DO 10.1101/gr.133926.111 
UL http://genome.cshlp.org/content/22/4/593.abstract 
AB 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.