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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, WK8 6 3
Zheng, H5
Li, S9
Chen, R4
Liu, X5
Li, Y5
Lee, NP3
Lee, WH6
Ariyaratne, PN6
Tennakoon, C8
Mulawadi, FH6
Wong, KF8 3
Liu, AM8 3
Poon, RT3
Fan, ST3
Chan, KL3
Gong, Z5
Hu, Y5
Lin, Z5
Wang, G5
Zhang, Q5
Barber, TD9
Chou, WC9
Aggarwal, A9
Hao, K4
Zhou, W4
Zhang, C4
Hardwick, J1 4
Buser, C4
Xu, J10
Kan, Z10
Dai, H4
Mao, M1 10
Reinhard, C9
Wang, J5 2
Luk, JM8 3 7
 
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
2013 Impact Factor: 29.648
2013 SCImago Journal Rankings: 24.052
 
DOIhttp://dx.doi.org/10.1038/ng.2295
 
ReferencesReferences in Scopus
 
DC FieldValue
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.eissn1546-1718
 
dc.identifier.epage769
 
dc.identifier.hkuros202939
 
dc.identifier.issn1061-4036
2013 Impact Factor: 29.648
2013 SCImago Journal Rankings: 24.052
 
dc.identifier.issue7
 
dc.identifier.pmid22634754
 
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
 
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Author Affiliations
  1. Asian Cancer Research Group, Inc.
  2. Københavns Universitet
  3. The University of Hong Kong
  4. Merck Research Laboratories
  5. Beijing Genomics Institute, Shenzhen
  6. Genome Institute of Singapore
  7. Roche RandD Center (China) Ltd.
  8. National University of Singapore
  9. Eli Lilly and Company
  10. Pfizer