Article: Array-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma

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TitleArray-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma
AuthorsPatil, MA1
Gütgemann, I2
Zhang, J1 6
Ho, C1
Cheung, ST5
Ginzinger, D1
Li, R6
Dykema, KJ4
So, S3
Fan, ST5
Kakar, S1
Furge, KA4
Büttner, R2
Chen, X1 6
Issue Date2005
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
CitationCarcinogenesis, 2005, v. 26 n. 12, p. 2050-2057 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgi178
AbstractHepatocellular carcinoma (HCC) is one of the major malignancies worldwide. We have previously characterized global gene expression patterns in HCC using microarrays. Here, we report the analysis of genomic DNA copy number among 49 HCC samples using BAC array-based comparative genomic hybridization (CGH). We observed recurrent and characteristic chromosomal aberrations, including frequent DNA copy number gains of 1q, 6p, 8q and 20q, and losses of 4q, 8p, 13q, 16q and 17p. We correlated gene expression with array CGH data, and identified a set of genes whose expression levels correlated with common chromosomal aberrations in HCC. Especially, we noticed that high expression of Jab1 in HCC significantly correlated with DNA copy number gain at 8q. Quantitative microsatellite analysis further confirmed DNA copy number gain at the Jab1 locus. Overexpression of Jab1 in HCC was also validated using real-time RT-PCR, and Jab1 protein levels were studied by immunohistochemistry on tissue microarrays. Functional analysis in HCC cell lines demonstrated that Jab1 may regulate HCC cell proliferation, thereby having a potential role in HCC development. In conclusion, this study shows that array-based CGH provides high resolution mapping of chromosomal aberrations in HCC, and demonstrates the feasibility of correlating array CGH data with gene expression data to identify novel oncogenes and tumor suppressor genes. © Oxford University Press 2005; all rights reserved.
ISSN0143-3334
2011 Impact Factor: 5.702
2011 SCImago Journal Rankings: 0.692
DOIhttp://dx.doi.org/10.1093/carcin/bgi178
ISI Accession Number IDWOS:000233415600003
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorPatil, MA
dc.contributor.authorGütgemann, I
dc.contributor.authorZhang, J
dc.contributor.authorHo, C
dc.contributor.authorCheung, ST
dc.contributor.authorGinzinger, D
dc.contributor.authorLi, R
dc.contributor.authorDykema, KJ
dc.contributor.authorSo, S
dc.contributor.authorFan, ST
dc.contributor.authorKakar, S
dc.contributor.authorFurge, KA
dc.contributor.authorBüttner, R
dc.contributor.authorChen, X
dc.date.accessioned2010-09-06T08:40:31Z
dc.date.available2010-09-06T08:40:31Z
dc.date.issued2005
dc.description.abstractHepatocellular carcinoma (HCC) is one of the major malignancies worldwide. We have previously characterized global gene expression patterns in HCC using microarrays. Here, we report the analysis of genomic DNA copy number among 49 HCC samples using BAC array-based comparative genomic hybridization (CGH). We observed recurrent and characteristic chromosomal aberrations, including frequent DNA copy number gains of 1q, 6p, 8q and 20q, and losses of 4q, 8p, 13q, 16q and 17p. We correlated gene expression with array CGH data, and identified a set of genes whose expression levels correlated with common chromosomal aberrations in HCC. Especially, we noticed that high expression of Jab1 in HCC significantly correlated with DNA copy number gain at 8q. Quantitative microsatellite analysis further confirmed DNA copy number gain at the Jab1 locus. Overexpression of Jab1 in HCC was also validated using real-time RT-PCR, and Jab1 protein levels were studied by immunohistochemistry on tissue microarrays. Functional analysis in HCC cell lines demonstrated that Jab1 may regulate HCC cell proliferation, thereby having a potential role in HCC development. In conclusion, this study shows that array-based CGH provides high resolution mapping of chromosomal aberrations in HCC, and demonstrates the feasibility of correlating array CGH data with gene expression data to identify novel oncogenes and tumor suppressor genes. © Oxford University Press 2005; all rights reserved.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationCarcinogenesis, 2005, v. 26 n. 12, p. 2050-2057 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgi178
dc.identifier.citeulike399067
dc.identifier.doihttp://dx.doi.org/10.1093/carcin/bgi178
dc.identifier.epage2057
dc.identifier.hkuros116907
dc.identifier.isiWOS:000233415600003
dc.identifier.issn0143-3334
2011 Impact Factor: 5.702
2011 SCImago Journal Rankings: 0.692
dc.identifier.issue12
dc.identifier.openurl
dc.identifier.pmid16000397
dc.identifier.scopuseid_2-s2.0-27944491603
dc.identifier.spage2050
dc.identifier.urihttp://hdl.handle.net/10722/83395
dc.identifier.volume26
dc.languageeng
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
dc.publisher.placeUnited Kingdom
dc.relation.ispartofCarcinogenesis
dc.relation.referencesReferences in Scopus
dc.rightsCarcinogenesis. Copyright © Oxford University Press.
dc.titleArray-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma
dc.typeArticle
Author Affiliations
  1. University of California, San Francisco
  2. Universität Bonn
  3. Stanford University
  4. Van Andel Research Institute
  5. The University of Hong Kong
  6. Peking University