title: Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma.
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.
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.
authors.forename: Ling-Hao
authors.initials: LH
authors.lastname: Zhao
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.
authors.forename: He-Xin
authors.initials: HX
authors.lastname: Yan
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.|School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Wei-Yang
authors.initials: WY
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.|Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong 999077, China.
authors.forename: Xi
authors.identifier: 0000-0002-5355-0773
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xue-Han
authors.initials: XH
authors.lastname: Zhuang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Lin
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.
authors.forename: Chen-Jie
authors.initials: CJ
authors.lastname: Qin
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Ze-Ya
authors.initials: ZY
authors.lastname: Pan
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Ruo-Yu
authors.initials: RY
authors.lastname: Wang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wen
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.
authors.forename: Gui-Shuai
authors.initials: GS
authors.lastname: Lv
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.
authors.forename: Hui-Lu
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wu
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Huang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.
authors.forename: Ming-Da
authors.initials: MD
authors.lastname: Wang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Cao
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi An 710032, China.
authors.forename: Ling
authors.identifier: 0000-0002-0175-0933
authors.initials: L
authors.lastname: Wang
authors.affiliation: Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong 999077, China.
authors.forename: Tin-Lap
authors.initials: TL
authors.lastname: Lee
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.
authors.forename: Ye-Xiong
authors.initials: YX
authors.lastname: Tan
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Sheng-Xian
authors.initials: SX
authors.lastname: Yuan
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Hou
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Qi-Fei
authors.initials: QF
authors.lastname: Tao
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Qin-Guo
authors.initials: QG
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xiu-Qing
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Wu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.|Department of Biology, University of Copenhagen, Ole Maaløes Vej 5,2200 Copenhagen, Denmark.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Huan-Ming
authors.initials: HM
authors.lastname: Yang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhou
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 200438, China.|State Key Laboratory of Oncogenes and Related Genes, Cancer Institute of Renji Hospital, Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology*; D002471:Cell Transformation, Neoplastic; D018899:CpG Islands; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015894:Genome, Human; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000235:genetics / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology*; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D016662:Virus Integration
chemical_list: D004279:DNA, Viral