Article: Integration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer
| Title | Integration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Fan, B1 4 Dachrut, S1 2 Coral, H1 Yuen, ST3 Chu, KM3 Law, S3 Zhang, L4 Ji, J4 Leung, SY3 Chen, X1 | ||||||
| Keywords | Complementary DNA Bacterial artificial chromosome Cancer cell Chromosome deletion Comparative genomic hybridization | ||||||
| Issue Date | 2012 | ||||||
| Publisher | Public 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?] DOI: http://dx.doi.org/10.1371/journal.pone.0029824 | ||||||
| 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. | ||||||
| ISSN | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 | ||||||
| DOI | http://dx.doi.org/10.1371/journal.pone.0029824 | ||||||
| ISI Accession Number ID | WOS:000305341000002
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. | ||||||
| PubMed Central ID | PMC3335165 | ||||||
| References | References in Scopus |
| dc.contributor.author | Fan, B | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Dachrut, S | ||||||
| dc.contributor.author | Coral, H | ||||||
| dc.contributor.author | Yuen, ST | ||||||
| dc.contributor.author | Chu, KM | ||||||
| dc.contributor.author | Law, S | ||||||
| dc.contributor.author | Zhang, L | ||||||
| dc.contributor.author | Ji, J | ||||||
| dc.contributor.author | Leung, SY | ||||||
| dc.contributor.author | Chen, X | ||||||
| dc.date.accessioned | 2012-05-29T06:14:44Z | ||||||
| dc.date.available | 2012-05-29T06:14:44Z | ||||||
| dc.date.issued | 2012 | ||||||
| dc.description.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. | ||||||
| dc.description.nature | published_or_final_version | ||||||
| dc.identifier.citation | Plos One, 2012, v. 7 n. 4 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0029824 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1371/journal.pone.0029824 | ||||||
| dc.identifier.hkuros | 205611 | ||||||
| dc.identifier.isi | WOS:000305341000002
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. | ||||||
| dc.identifier.issn | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 | ||||||
| dc.identifier.issue | 4 | ||||||
| dc.identifier.pmcid | PMC3335165 | ||||||
| dc.identifier.pmid | 22539939 | ||||||
| dc.identifier.scopus | eid_2-s2.0-84859967040 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/148694 | ||||||
| dc.identifier.volume | 7 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | PLoS ONE | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||
| dc.subject | Complementary DNA | ||||||
| dc.subject | Bacterial artificial chromosome | ||||||
| dc.subject | Cancer cell | ||||||
| dc.subject | Chromosome deletion | ||||||
| dc.subject | Comparative genomic hybridization | ||||||
| dc.title | Integration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer | ||||||
| dc.type | Article |
Author Affiliations
- University of California, San Francisco
- Khon Kaen University
- The University of Hong Kong
- Peking University