M. Wolf, S. Mousses, S. Hautaniemi, R. Karhu, P. Huusko, M. Allinen, A. Elkahloun, O. Monni, Yidong Chen, A. Kallioniemi, O. Kallioniemi
{"title":"利用cDNA微阵列上的CGH对人前列腺癌基因拷贝数变化的高分辨率分析:拷贝数对基因表达的影响。","authors":"M. Wolf, S. Mousses, S. Hautaniemi, R. Karhu, P. Huusko, M. Allinen, A. Elkahloun, O. Monni, Yidong Chen, A. Kallioniemi, O. Kallioniemi","doi":"10.1593/NEO.03439","DOIUrl":null,"url":null,"abstract":"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 classic chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, and their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13q, and gains at 1q and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, and 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, and 17q (losses), and at 3q, 5p, and 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.","PeriodicalId":48716,"journal":{"name":"Neoplasia","volume":null,"pages":null},"PeriodicalIF":6.3000,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"141","resultStr":"{\"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.\",\"authors\":\"M. Wolf, S. Mousses, S. Hautaniemi, R. Karhu, P. Huusko, M. Allinen, A. Elkahloun, O. Monni, Yidong Chen, A. Kallioniemi, O. Kallioniemi\",\"doi\":\"10.1593/NEO.03439\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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 classic chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, and their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13q, and gains at 1q and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, and 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. 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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 lines. CGH microarrays identified most of the alterations detected by classic chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, and their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13q, and gains at 1q and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, and 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, and 17q (losses), and at 3q, 5p, and 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.
期刊介绍:
Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.