title: The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients.
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.
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech Inc, South San Francisco, California 94080, USA.
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Jiang
authors.forename: Suchit
authors.initials: S
authors.lastname: Jhunjhunwala
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Peter M
authors.initials: PM
authors.lastname: Haverty
authors.forename: Michael I
authors.initials: MI
authors.lastname: Kennemer
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Guan
authors.forename: William
authors.initials: W
authors.lastname: Lee
authors.forename: Paolo
authors.initials: P
authors.lastname: Carnevali
authors.forename: Jeremy
authors.initials: J
authors.lastname: Stinson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Johnson
authors.forename: Jingyu
authors.initials: J
authors.lastname: Diao
authors.forename: Stacy
authors.initials: S
authors.lastname: Yeung
authors.forename: Adrian
authors.initials: A
authors.lastname: Jubb
authors.forename: Weilan
authors.initials: W
authors.lastname: Ye
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Wu
authors.forename: Sharookh B
authors.initials: SB
authors.lastname: Kapadia
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: de Sauvage
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gentleman
authors.forename: Howard M
authors.initials: HM
authors.lastname: Stern
authors.forename: Somasekar
authors.initials: S
authors.lastname: Seshagiri
authors.forename: Krishna P
authors.initials: KP
authors.lastname: Pant
authors.forename: Zora
authors.initials: Z
authors.lastname: Modrusan
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Ballinger
authors.forename: Zemin
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics*; D006509:Hepatitis B / Q000235:genetics* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D017422:Sequence Analysis, DNA / Q000379:methods; D059467:Transcriptome / Q000235:genetics; D016662:Virus Integration / Q000235:genetics*