title: Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular and Cell Biology, Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Spain. raquel.bermudo@cid.csic.es
authors.forename: Raquel
authors.initials: R
authors.lastname: Bermudo
authors.forename: David
authors.initials: D
authors.lastname: Abia
authors.forename: Berta
authors.initials: B
authors.lastname: Ferrer
authors.forename: Iracema
authors.initials: I
authors.lastname: Nayach
authors.forename: Alberto
authors.initials: A
authors.lastname: Benguria
authors.forename: Angel
authors.initials: A
authors.lastname: Zaballos
authors.forename: Javier
authors.initials: J
authors.lastname: del Rey
authors.forename: Rosa
authors.initials: R
authors.lastname: Miró
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-A
authors.forename: Angel R
authors.initials: AR
authors.lastname: Ortiz
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Fernández
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Thomson
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009693:Nucleic Acid Hybridization; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic