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Article: Integration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer

TitleIntegration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer
Authors
KeywordsComplementary DNA
Bacterial artificial chromosome
Cancer cell
Chromosome deletion
Comparative genomic hybridization
Issue Date2012
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2012, v. 7 n. 4 How to Cite?
Abstract
Background: Genomic instability with frequent DNA copy number alterations is one of the key hallmarks of carcinogenesis. The chromosomal regions with frequent DNA copy number gain and loss in human gastric cancer are still poorly defined. It remains unknown how the DNA copy number variations contributes to the changes of gene expression profiles, especially on the global level. Principal Findings: We analyzed DNA copy number alterations in 64 human gastric cancer samples and 8 gastric cancer cell lines using bacterial artificial chromosome (BAC) arrays based comparative genomic hybridization (aCGH). Statistical analysis was applied to correlate previously published gene expression data obtained from cDNA microarrays with corresponding DNA copy number variation data to identify candidate oncogenes and tumor suppressor genes. We found that gastric cancer samples showed recurrent DNA copy number variations, including gains at 5p, 8q, 20p, 20q, and losses at 4q, 9p, 18q, 21q. The most frequent regions of amplification were 20q12 (7/72), 20q12-20q13.1 (12/72), 20q13.1-20q13.2 (11/72) and 20q13.2-20q13.3 (6/72). The most frequent deleted region was 9p21 (8/72). Correlating gene expression array data with aCGH identified 321 candidate oncogenes, which were overexpressed and showed frequent DNA copy number gains; and 12 candidate tumor suppressor genes which were down-regulated and showed frequent DNA copy number losses in human gastric cancers. Three networks of significantly expressed genes in gastric cancer samples were identified by ingenuity pathway analysis. Conclusions: This study provides insight into DNA copy number variations and their contribution to altered gene expression profiles during human gastric cancer development. It provides novel candidate driver oncogenes or tumor suppressor genes for human gastric cancer, useful pathway maps for the future understanding of the molecular pathogenesis of this malignancy, and the construction of new therapeutic targets. © 2012 Fan et al.
Persistent Identifierhttp://hdl.handle.net/10722/148694
ISSN
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University of California Cancer Research Coordinate Committee
China Scholarship Council2010601079
Funding Information:

This work is supported by the funding provided by University of California Cancer Research Coordinate Committee to XC. BF is supported by China Scholarship Council Contract No.2010601079. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

Author Affiliations
  1. University of California, San Francisco
  2. Khon Kaen University
  3. The University of Hong Kong
  4. Peking University
DC FieldValueLanguage
dc.contributor.authorFan, Ben_HK
dc.contributor.authorDachrut, Sen_HK
dc.contributor.authorCoral, Hen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorChu, KMen_HK
dc.contributor.authorLaw, Sen_HK
dc.contributor.authorZhang, Len_HK
dc.contributor.authorJi, Jen_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorChen, Xen_HK
dc.date.accessioned2012-05-29T06:14:44Z-
dc.date.available2012-05-29T06:14:44Z-
dc.date.issued2012en_HK
dc.identifier.citationPlos One, 2012, v. 7 n. 4en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148694-
dc.description.abstractBackground: Genomic instability with frequent DNA copy number alterations is one of the key hallmarks of carcinogenesis. The chromosomal regions with frequent DNA copy number gain and loss in human gastric cancer are still poorly defined. It remains unknown how the DNA copy number variations contributes to the changes of gene expression profiles, especially on the global level. Principal Findings: We analyzed DNA copy number alterations in 64 human gastric cancer samples and 8 gastric cancer cell lines using bacterial artificial chromosome (BAC) arrays based comparative genomic hybridization (aCGH). Statistical analysis was applied to correlate previously published gene expression data obtained from cDNA microarrays with corresponding DNA copy number variation data to identify candidate oncogenes and tumor suppressor genes. We found that gastric cancer samples showed recurrent DNA copy number variations, including gains at 5p, 8q, 20p, 20q, and losses at 4q, 9p, 18q, 21q. The most frequent regions of amplification were 20q12 (7/72), 20q12-20q13.1 (12/72), 20q13.1-20q13.2 (11/72) and 20q13.2-20q13.3 (6/72). The most frequent deleted region was 9p21 (8/72). Correlating gene expression array data with aCGH identified 321 candidate oncogenes, which were overexpressed and showed frequent DNA copy number gains; and 12 candidate tumor suppressor genes which were down-regulated and showed frequent DNA copy number losses in human gastric cancers. Three networks of significantly expressed genes in gastric cancer samples were identified by ingenuity pathway analysis. Conclusions: This study provides insight into DNA copy number variations and their contribution to altered gene expression profiles during human gastric cancer development. It provides novel candidate driver oncogenes or tumor suppressor genes for human gastric cancer, useful pathway maps for the future understanding of the molecular pathogenesis of this malignancy, and the construction of new therapeutic targets. © 2012 Fan et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectComplementary DNA-
dc.subjectBacterial artificial chromosome-
dc.subjectCancer cell-
dc.subjectChromosome deletion-
dc.subjectComparative genomic hybridization-
dc.titleIntegration of DNA copy number alterations and transcriptional expression analysis in human gastric canceren_HK
dc.typeArticleen_HK
dc.identifier.emailChu, KM: chukm@hkucc.hku.hken_HK
dc.identifier.emailLaw, S: slaw@hku.hken_HK
dc.identifier.emailLeung, SY: suetyi@hkucc.hku.hken_HK
dc.identifier.authorityChu, KM=rp00435en_HK
dc.identifier.authorityLaw, S=rp00437en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0029824en_HK
dc.identifier.pmid22539939-
dc.identifier.pmcidPMC3335165-
dc.identifier.scopuseid_2-s2.0-84859967040en_HK
dc.identifier.hkuros205611-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84859967040&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume7en_HK
dc.identifier.issue4en_HK
dc.identifier.isiWOS:000305341000002-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridFan, B=55192875100en_HK
dc.identifier.scopusauthoridDachrut, S=25631821700en_HK
dc.identifier.scopusauthoridCoral, H=55193092100en_HK
dc.identifier.scopusauthoridYuen, ST=7103160927en_HK
dc.identifier.scopusauthoridChu, KM=7402453538en_HK
dc.identifier.scopusauthoridLaw, S=7202241293en_HK
dc.identifier.scopusauthoridZhang, L=35782676300en_HK
dc.identifier.scopusauthoridJi, J=7201362473en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK
dc.identifier.scopusauthoridChen, X=8978110800en_HK

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