title: Distinct hepatitis B virus integration patterns in hepatocellular carcinoma and adjacent normal liver tissue.
abstract: Infection by the hepatitis B virus (HBV) is one of the main etiologies of hepatocellular carcinoma (HCC). During chronic infection, HBV DNA can integrate into the human genome, and this has been postulated as a possible mechanism of HBV-induced HCC. In this study we used 2199 HBV integration sites from Dr.VIS v2.0 and mapped them to the human genome (hg19) to obtain viral integration sites (VIS) related to protein-coding and non-protein-coding genes. In total, we found 1,377 and 767 VIS within close proximity to protein coding genes and noncoding genes, respectively. Genes affected more than two times included 23.1% of protein-coding genes and 24.7% of long noncoding RNAs (lncRNA). Only 4.8% of VIS were shared between HCC and non-tumor tissues. HBV integrations were more common in chromosomes 5, 8, 10, and 19 in HCC tissue and chromosomes 1 and 2 in non-tumorous tissue. The number of integration sites on each chromosome correlated with the number of fragile sites in non-tumorous tissue but not in HCC tissue. Functional enrichment analysis of the protein-coding genes containing or in close proximity to HBV integration sites in HCC tissue showed an enrichment of cancer related gene ontology terms. Additionally, the most frequently associated lncRNA genes were related to telomere maintenance, protein modification processes, and chromosome localization. Thus, HBV may have preferred integration sites in the human genome that serve a critical role in HCC development. These results show that HCC treatment may benefit from the development of next generation anti-viral therapies.
authors.affiliation: Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Liangcai
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Anqiang
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Xueshuai
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Medicine, Liver Center and The Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.|Department of Surgery, Liver Center and The Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Medicine, Liver Center and The Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.|Department of Surgery, Liver Center and The Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
authors.affiliation: Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Xinting
authors.initials: X
authors.lastname: Sang
authors.affiliation: Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.|Center of Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhao
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000821:virology*; D043283:Chromosome Fragile Sites; D002874:Chromosome Mapping; D004279:DNA, Viral / Q000032:analysis*; D063990:Gene Ontology; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000821:virology*; D008113:Liver Neoplasms / Q000821:virology*; D062085:RNA, Long Noncoding / Q000235:genetics; D016662:Virus Integration
chemical_list: D004279:DNA, Viral; D062085:RNA, Long Noncoding