Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

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, Ruo-Yu Wang, Yun Yang, Wen Wen, Gui-Shuai Lv, Hui-Lu Zhang, Han Wu, Shuai Huang, Ming-Da Wang, Liang Tang, Hong-Zhi Cao, Ling Wang, Tin-Lap Lee, Hui Jiang, Ye-Xiong Tan, Sheng-Xian Yuan, Guo-Jun Hou, Qi-Fei Tao, Qin-Guo Xu, Xiu-Qing Zhang, Meng-Chao Wu, Xun Xu, Jun Wang, Huan-Ming Yang (), Wei-Ping Zhou () and Hong-Yang Wang ()
Additional contact information
Ling-Hao Zhao: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
Xiao Liu: BGI-Shenzhen
He-Xin Yan: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
Wei-Yang Li: BGI-Shenzhen
Xi Zeng: BGI-Shenzhen
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
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
Gui-Shuai Lv: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
Hui-Lu Zhang: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
Han Wu: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
Shuai Huang: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
Ming-Da Wang: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
Liang Tang: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
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
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
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

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12992

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