Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes
Introduction: Testicular germ cell tumors of adolescent and young adult men (TGCTs) generally have near triploid and complex karyotypes. The actual genes driving the tumorigenesis remain essentially to be identified. Materials and Methods: To determine the detailed DNA copy number changes, and inves...
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| Format: | Article |
| Language: | English |
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Wiley
2006-01-01
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| Series: | Cellular Oncology |
| Online Access: | http://dx.doi.org/10.1155/2006/219786 |
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| author | Rolf I. Skotheim Reija Autio Guro E. Lind Sigrid M. Kraggerud Peter W. Andrews Outi Monni Olli Kallioniemi Ragnhild A. Lothe |
| author_facet | Rolf I. Skotheim Reija Autio Guro E. Lind Sigrid M. Kraggerud Peter W. Andrews Outi Monni Olli Kallioniemi Ragnhild A. Lothe |
| author_sort | Rolf I. Skotheim |
| collection | DOAJ |
| description | Introduction: Testicular germ cell tumors of adolescent and young adult men (TGCTs) generally have near triploid and complex karyotypes. The actual genes driving the tumorigenesis remain essentially to be identified. Materials and Methods: To determine the detailed DNA copy number changes, and investigate their impact on gene expression levels, we performed an integrated microarray profiling of TGCT genomes and transcriptomes. We analyzed 17 TGCTs, three precursor lesions, and the embryonal carcinoma cell lines, NTERA2 and 2102Ep, by comparative genomic hybridization microarrays (array-CGH), and integrated the data with transcriptome profiles of the same samples. Results: The gain of chromosome arm 12p was, as expected, the most common aberration, and we found CCND2, CD9, GAPD, GDF3, NANOG, and TEAD4 to be the therein most highly over-expressed genes. Additional frequent genomic aberrations revealed some shorter chromosomal segments, which are novel to TGCT, as well as known aberrations for which we here refined boundaries. These include gains from 7p15.2 and 21q22.2, and losses of 4p16.3 and 22q13.3. Integration of DNA copy number information to gene expression profiles identified that BRCC3, FOS, MLLT11, NES, and RAC1 may act as novel oncogenes in TGCT. Similarly, DDX26, ERCC5, FZD4, NME4, OPTN, and RB1 were both lost and under-expressed genes, and are thus putative TGCT suppressor genes. Conclusion: This first genome-wide integrated array-CGH and gene expression profiling of TGCT provides novel insights into the genome biology underlying testicular tumorigenesis. |
| format | Article |
| id | doaj-art-5a31bf23f78b4b899e98a218ce24d710 |
| institution | Kabale University |
| issn | 1570-5870 1875-8606 |
| language | English |
| publishDate | 2006-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cellular Oncology |
| spelling | doaj-art-5a31bf23f78b4b899e98a218ce24d7102025-02-03T07:24:41ZengWileyCellular Oncology1570-58701875-86062006-01-01285-631532610.1155/2006/219786Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression ChangesRolf I. Skotheim0Reija Autio1Guro E. Lind2Sigrid M. Kraggerud3Peter W. Andrews4Outi Monni5Olli Kallioniemi6Ragnhild A. Lothe7Department of Cancer Prevention, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, NorwayInstitute of Signal Processing, Tampere University of Technology, Tampere, FinlandDepartment of Cancer Prevention, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, NorwayDepartment of Cancer Prevention, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, NorwayDepartment of Biomedical Science, University of Sheffield, Sheffield, United KingdomBiomedicum Biochip Center and Institute of Biomedicine, BioMedicum Helsinki, University of Helsinki, Helsinki, FinlandMedical Biotechnology Group, VTT Technical Research Centre of Finland and University of Turku, Turku, FinlandDepartment of Cancer Prevention, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, NorwayIntroduction: Testicular germ cell tumors of adolescent and young adult men (TGCTs) generally have near triploid and complex karyotypes. The actual genes driving the tumorigenesis remain essentially to be identified. Materials and Methods: To determine the detailed DNA copy number changes, and investigate their impact on gene expression levels, we performed an integrated microarray profiling of TGCT genomes and transcriptomes. We analyzed 17 TGCTs, three precursor lesions, and the embryonal carcinoma cell lines, NTERA2 and 2102Ep, by comparative genomic hybridization microarrays (array-CGH), and integrated the data with transcriptome profiles of the same samples. Results: The gain of chromosome arm 12p was, as expected, the most common aberration, and we found CCND2, CD9, GAPD, GDF3, NANOG, and TEAD4 to be the therein most highly over-expressed genes. Additional frequent genomic aberrations revealed some shorter chromosomal segments, which are novel to TGCT, as well as known aberrations for which we here refined boundaries. These include gains from 7p15.2 and 21q22.2, and losses of 4p16.3 and 22q13.3. Integration of DNA copy number information to gene expression profiles identified that BRCC3, FOS, MLLT11, NES, and RAC1 may act as novel oncogenes in TGCT. Similarly, DDX26, ERCC5, FZD4, NME4, OPTN, and RB1 were both lost and under-expressed genes, and are thus putative TGCT suppressor genes. Conclusion: This first genome-wide integrated array-CGH and gene expression profiling of TGCT provides novel insights into the genome biology underlying testicular tumorigenesis.http://dx.doi.org/10.1155/2006/219786 |
| spellingShingle | Rolf I. Skotheim Reija Autio Guro E. Lind Sigrid M. Kraggerud Peter W. Andrews Outi Monni Olli Kallioniemi Ragnhild A. Lothe Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes Cellular Oncology |
| title | Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes |
| title_full | Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes |
| title_fullStr | Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes |
| title_full_unstemmed | Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes |
| title_short | Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes |
| title_sort | novel genomic aberrations in testicular germ cell tumors by array cgh and associated gene expression changes |
| url | http://dx.doi.org/10.1155/2006/219786 |
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