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| Home > Articles > Published articles > Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer |
| Home > Articles > Published articles > Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer |
(Centro de Biología Molecular Severo Ochoa) (Centro Nacional de Biotecnología. Departamento de Inmunología y Oncología) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Institut d'Investigacions Biomèdiques August Pi i Sunyer)| Date: | 2008 |
| Abstract: | Background: transcriptional profiling of prostate cancer (PC) has unveiled new markers of neoplasia and allowed insights into mechanisms underlying this disease. Genomewide analyses have also identified new chromosomal abnormalities associated with PC. The combination of both classes of data for the same sample cohort might provide better criteria for identifying relevant factors involved in neoplasia. Here we describe transcriptional signatures identifying distinct normal and tumoral prostate tissue compartments, and the inference and demonstration of a new, highly recurrent copy number gain on chromosome 17q25. 3. - Methods: we have applied transcriptional profiling to tumoral and non-tumoral prostate samples with relatively homogeneous epithelial representations as well as pure stromal tissue from peripheral prostate and cultured cell lines, followed by quantitative RT-PCR validations and immunohistochemical analysis. In addition, we have performed in silico colocalization analysis of co-regulated genes and validation by fluorescent in situ hybridization (FISH). - Results: the transcriptomic analysis has allowed us to identify signatures corresponding to non-tumoral luminal and tumoral epithelium, basal epithelial cells, and prostate stromal tissue. In addition, in silico analysis of co-regulated expression of physically linked genes has allowed us to predict the occurrence of a copy number gain at chromosomal region 17q25. 3. This computational inference was validated by fluorescent in situ hybridization, which showed gains in this region in over 65% of primary and metastatic tumoral samples. - Conclusion: our approach permits to directly link gene copy number variations with transcript co-regulation in association with neoplastic states. Therefore, transcriptomic studies of carefully selected samples can unveil new diagnostic markers and transcriptional signatures highly specific of PC, and lead to the discovery of novel genomic abnormalities that may provide additional insights into the causes and mechanisms of prostate cancer. |
| Grants: | Ministerio de Educación y Ciencia GEN2001-4856-C13 Ministerio de Educación y Ciencia GEN2001-4856-C10 Ministerio de Educación y Ciencia SAF2005-05109 Instituto de Salud Carlos III PI020231 |
| Note: | Altres ajuts: the Fundació Marató TV3, the Red Temática de Cáncer of the Instituto Carlos III (RET2039) and the Fundación Ramón Areces |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Prostatic neoplasms |
| Published in: | BMC Cancer, Vol. 8 (2008) , art. 315, ISSN 1471-2407 |
