Article: Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma

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TitleGenome-wide survey of recurrent HBV integration in hepatocellular carcinoma
AuthorsSung, WK4 6 8
Zheng, H5
Li, S9
Chen, R3
Liu, X5
Li, Y5
Lee, NP4
Lee, WH6
Ariyaratne, PN6
Tennakoon, C8
Mulawadi, FH6
Wong, KF4 8
Liu, AM4 8
Poon, RT4
Fan, ST4
Chan, KL4
Gong, Z5
Hu, Y5
Lin, Z5
Wang, G5
Zhang, Q5
Barber, TD9
Chou, WC9
Aggarwal, A9
Hao, K3
Zhou, W3
Zhang, C3
Hardwick, J1 3
Buser, C3
Xu, J10
Kan, Z10
Dai, H3
Mao, M1 10
Reinhard, C9
Wang, J2 5
Luk, JM4 7 8
Issue Date2012
PublisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
CitationNature Genetics, 2012, v. 44 n. 7, p. 765-769 [How to Cite?]
DOI: http://dx.doi.org/10.1038/ng.2295
AbstractTo survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) than in adjacent liver tissues (30.7%). Copy-number variations (CNVs) were significantly increased at HBV breakpoint locations where chromosomal instability was likely induced. Approximately 40% of HBV breakpoints within the HBV genome were located within a 1,800-bp region where the viral enhancer, X gene and core gene are located. We also identified recurrent HBV integration events (in ≥4 HCCs) that were validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and putative cancer-related TERT, MLL4 and CCNE1 genes, which showed upregulated gene expression in tumor versus normal tissue. We also report evidence that suggests that the number of HBV integrations is associated with patient survival. © 2012 Nature America, Inc. All rights reserved.
ISSN1061-4036
2011 Impact Factor: 35.532
2011 SCImago Journal Rankings: 8.923
DOIhttp://dx.doi.org/10.1038/ng.2295
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorSung, WK
dc.contributor.authorZheng, H
dc.contributor.authorLi, S
dc.contributor.authorChen, R
dc.contributor.authorLiu, X
dc.contributor.authorLi, Y
dc.contributor.authorLee, NP
dc.contributor.authorLee, WH
dc.contributor.authorAriyaratne, PN
dc.contributor.authorTennakoon, C
dc.contributor.authorMulawadi, FH
dc.contributor.authorWong, KF
dc.contributor.authorLiu, AM
dc.contributor.authorPoon, RT
dc.contributor.authorFan, ST
dc.contributor.authorChan, KL
dc.contributor.authorGong, Z
dc.contributor.authorHu, Y
dc.contributor.authorLin, Z
dc.contributor.authorWang, G
dc.contributor.authorZhang, Q
dc.contributor.authorBarber, TD
dc.contributor.authorChou, WC
dc.contributor.authorAggarwal, A
dc.contributor.authorHao, K
dc.contributor.authorZhou, W
dc.contributor.authorZhang, C
dc.contributor.authorHardwick, J
dc.contributor.authorBuser, C
dc.contributor.authorXu, J
dc.contributor.authorKan, Z
dc.contributor.authorDai, H
dc.contributor.authorMao, M
dc.contributor.authorReinhard, C
dc.contributor.authorWang, J
dc.contributor.authorLuk, JM
dc.date.accessioned2012-08-16T05:59:36Z
dc.date.available2012-08-16T05:59:36Z
dc.date.issued2012
dc.description.abstractTo survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) than in adjacent liver tissues (30.7%). Copy-number variations (CNVs) were significantly increased at HBV breakpoint locations where chromosomal instability was likely induced. Approximately 40% of HBV breakpoints within the HBV genome were located within a 1,800-bp region where the viral enhancer, X gene and core gene are located. We also identified recurrent HBV integration events (in ≥4 HCCs) that were validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and putative cancer-related TERT, MLL4 and CCNE1 genes, which showed upregulated gene expression in tumor versus normal tissue. We also report evidence that suggests that the number of HBV integrations is associated with patient survival. © 2012 Nature America, Inc. All rights reserved.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationNature Genetics, 2012, v. 44 n. 7, p. 765-769 [How to Cite?]
DOI: http://dx.doi.org/10.1038/ng.2295
dc.identifier.citeulike10717104
dc.identifier.doihttp://dx.doi.org/10.1038/ng.2295
dc.identifier.epage769
dc.identifier.hkuros202939
dc.identifier.issn1061-4036
2011 Impact Factor: 35.532
2011 SCImago Journal Rankings: 8.923
dc.identifier.issue7
dc.identifier.scopuseid_2-s2.0-84862999344
dc.identifier.spage765
dc.identifier.urihttp://hdl.handle.net/10722/159928
dc.identifier.volume44
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
dc.publisher.placeUnited States
dc.relation.ispartofNature Genetics
dc.relation.referencesReferences in Scopus
dc.titleGenome-wide survey of recurrent HBV integration in hepatocellular carcinoma
dc.typeArticle
Author Affiliations
  1. Asian Cancer Research Group, Inc.
  2. Københavns Universitet
  3. Merck Research Laboratories
  4. The University of Hong Kong
  5. Beijing Genomics Institute, Shenzhen
  6. Genome Institute of Singapore
  7. null
  8. National University of Singapore
  9. Eli Lilly and Company
  10. Pfizer