High-Resolution Analysis of Gene Copy Number Alterations in Human Prostate Cancer Using CGH on cDNA Microarrays: Impact of Copy Number on Gene Expression
Identification of target genes for genetic rearrangements in prostate cancer and the impact of copy number changes on gene expression are currently not well understood. Here, we applied high-resolution comparative genomic hybridization (CGH) on cDNA microarrays for analysis of prostate cancer cell l...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2004-05-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S147655860480071X |
| _version_ | 1818582798373486592 |
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| author | Maija Wolf Spyro Mousses Sampsa Hautaniemi Ritva Karhu Pia Huusko Minna Allinen Abdel Elkahloun Outi Monni Yidong Chen Anne Kallioniemi Olli-P Kallioniemi |
| author_facet | Maija Wolf Spyro Mousses Sampsa Hautaniemi Ritva Karhu Pia Huusko Minna Allinen Abdel Elkahloun Outi Monni Yidong Chen Anne Kallioniemi Olli-P Kallioniemi |
| author_sort | Maija Wolf |
| collection | DOAJ |
| description | Identification of target genes for genetic rearrangements in prostate cancer and the impact of copy number changes on gene expression are currently not well understood. Here, we applied high-resolution comparative genomic hybridization (CGH) on cDNA microarrays for analysis of prostate cancer cell lines. CGH microarrays identified most of the alterations detected by classical chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13% and gains at iq and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, 74-76 Mbp from the p-telomere), which matched with minimal regions of loss seen in extensive loss of heterozygosity mapping studies of large numbers of tumors. Previously unreported recurrent changes were found at 2p, 2q, 3p, 17q (losses), at 3q, 5p, 6p (gains). Integration of genomic and transcriptomic data revealed the role of individual candidate target genes for genomic alterations as well as a highly significant (P < .0001) overall association between copy number levels and the percentage of differentially expressed genes. Across the genome, the overall impact of copy number on gene expression levels was, to a large extent, attributable to low-level gains and losses of copy number, corresponding to common deletions and gains of often large chromosomal regions. |
| first_indexed | 2024-12-16T07:55:07Z |
| format | Article |
| id | doaj.art-c3db72a623b54bb9a18aa4eeada48002 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-16T07:55:07Z |
| publishDate | 2004-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-c3db72a623b54bb9a18aa4eeada480022022-12-21T22:38:45ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022004-05-016324024710.1593/neo.03439High-Resolution Analysis of Gene Copy Number Alterations in Human Prostate Cancer Using CGH on cDNA Microarrays: Impact of Copy Number on Gene ExpressionMaija Wolf0Spyro Mousses1Sampsa Hautaniemi2Ritva Karhu3Pia Huusko4Minna Allinen5Abdel Elkahloun6Outi Monni7Yidong Chen8Anne Kallioniemi9Olli-P Kallioniemi10Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, FinlandTranslational Genomics Research Institute, Gaithersburg, MD 20878-1762, USAInstitute of Signal Processing, Tampere University of Technology, Tampere FIN-33101, FinlandLaboratory of Cancer Genetics, Tampere University Hospital and Institute of Medical Technology, University of Tampere, Tampere FIN-33520, FinlandTranslational Genomics Research Institute, Gaithersburg, MD 20878-1762, USACancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USACancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USABiomedicum Biochip Center, University of Helsinki, Helsinki FIN-00014, FinlandCancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Cancer Genetics, Tampere University Hospital and Institute of Medical Technology, University of Tampere, Tampere FIN-33520, FinlandMedical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, FinlandIdentification of target genes for genetic rearrangements in prostate cancer and the impact of copy number changes on gene expression are currently not well understood. Here, we applied high-resolution comparative genomic hybridization (CGH) on cDNA microarrays for analysis of prostate cancer cell lines. CGH microarrays identified most of the alterations detected by classical chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13% and gains at iq and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, 74-76 Mbp from the p-telomere), which matched with minimal regions of loss seen in extensive loss of heterozygosity mapping studies of large numbers of tumors. Previously unreported recurrent changes were found at 2p, 2q, 3p, 17q (losses), at 3q, 5p, 6p (gains). Integration of genomic and transcriptomic data revealed the role of individual candidate target genes for genomic alterations as well as a highly significant (P < .0001) overall association between copy number levels and the percentage of differentially expressed genes. Across the genome, the overall impact of copy number on gene expression levels was, to a large extent, attributable to low-level gains and losses of copy number, corresponding to common deletions and gains of often large chromosomal regions.http://www.sciencedirect.com/science/article/pii/S147655860480071XCopy number alterationprostate cancergene expressioncDNA microarrayCGH microarray |
| spellingShingle | Maija Wolf Spyro Mousses Sampsa Hautaniemi Ritva Karhu Pia Huusko Minna Allinen Abdel Elkahloun Outi Monni Yidong Chen Anne Kallioniemi Olli-P Kallioniemi High-Resolution Analysis of Gene Copy Number Alterations in Human Prostate Cancer Using CGH on cDNA Microarrays: Impact of Copy Number on Gene Expression Neoplasia: An International Journal for Oncology Research Copy number alteration prostate cancer gene expression cDNA microarray CGH microarray |
| title | High-Resolution Analysis of Gene Copy Number Alterations in Human Prostate Cancer Using CGH on cDNA Microarrays: Impact of Copy Number on Gene Expression |
| title_full | High-Resolution Analysis of Gene Copy Number Alterations in Human Prostate Cancer Using CGH on cDNA Microarrays: Impact of Copy Number on Gene Expression |
| title_fullStr | High-Resolution Analysis of Gene Copy Number Alterations in Human Prostate Cancer Using CGH on cDNA Microarrays: Impact of Copy Number on Gene Expression |
| title_full_unstemmed | High-Resolution Analysis of Gene Copy Number Alterations in Human Prostate Cancer Using CGH on cDNA Microarrays: Impact of Copy Number on Gene Expression |
| title_short | High-Resolution Analysis of Gene Copy Number Alterations in Human Prostate Cancer Using CGH on cDNA Microarrays: Impact of Copy Number on Gene Expression |
| title_sort | high resolution analysis of gene copy number alterations in human prostate cancer using cgh on cdna microarrays impact of copy number on gene expression |
| topic | Copy number alteration prostate cancer gene expression cDNA microarray CGH microarray |
| url | http://www.sciencedirect.com/science/article/pii/S147655860480071X |
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