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Open Access 01-12-2008 | Research article

Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer

Authors: Raquel Bermudo, David Abia, Berta Ferrer, Iracema Nayach, Alberto Benguria, Ángel Zaballos, Javier del Rey, Rosa Miró, Elías Campo, Carlos Martínez-A, Ángel R Ortiz, Pedro L Fernández, Timothy M Thomson

Published in: BMC Cancer | Issue 1/2008

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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/8/315/prepub

Title: Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer
Authors: Raquel Bermudo
David Abia
Berta Ferrer
Iracema Nayach
Alberto Benguria
Ángel Zaballos
Javier del Rey
Rosa Miró
Elías Campo
Carlos Martínez-A
Ángel R Ortiz
Pedro L Fernández
Timothy M Thomson
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-8-315

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