title: NCOA2 is a candidate target gene of 8q gain associated with clinically aggressive prostate cancer.
abstract: Prostate carcinomas harboring 8q gains are associated with poor clinical outcome, but the target genes of this genomic alteration remain to be unveiled. In this study, we aimed to identify potential 8q target genes associated with clinically aggressive prostate cancer (PCa) using fluorescence in situ hybridization (FISH), genome-wide mRNA expression, and protein expression analyses. Using FISH, we first characterized the relative copy number of 8q (assessed with MYC flanking probes) of a series of 50 radical prostatectomy specimens, with available global gene expression data and typed for E26 transformation specific (ETS) rearrangements, and then compared the gene expression profile of PCa subsets with and without 8q24 gain using Significance Analysis of Microarrays. In the subset of tumors with ERG fusion genes (ERG+), five genes were identified as significantly overexpressed (false discovery rate [FDR], ≤ 5%) in tumors with relative 8q24 gain, namely VN1R1, ZNF417, CDON, IKZF2, and NCOA2. Of these, only NCOA2 is located in 8q (8q13.3), showing a statistically higher mRNA expression in the subgroup with relative 8q gain, both in the ERG+ subgroup and in the whole series (P = 0.000152 and P = 0.008, respectively). Combining all the cases with NCOA2 overexpression, either at the mRNA or at the protein level, we identified a group of tumors with NCOA2 copy-number increase, independently of ETS status and relative 8q24 gain. Furthermore, for the first time, we detected a structural rearrangement involving NCOA2 in PCa. These findings warrant further studies with larger series to evaluate if NCOA2 relative copy-number gain presents prognostic value independently of the well-established poor prognosis associated with MYC relative copy-number gain.
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.|Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Silva
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.|Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
authors.forename: João D
authors.initials: JD
authors.lastname: Barros-Silva
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Vieira
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Lisboa
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
authors.forename: Lurdes
authors.initials: L
authors.lastname: Torres
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.|Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
authors.forename: Cecília
authors.initials: C
authors.lastname: Correia
authors.affiliation: Cancer Biology and Epigenetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
authors.forename: Márcia
authors.initials: M
authors.lastname: Vieira-Coimbra
authors.affiliation: Cancer Biology and Epigenetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
authors.forename: Ana T
authors.initials: AT
authors.lastname: Martins
authors.affiliation: Cancer Biology and Epigenetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.|Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Carmen
authors.initials: C
authors.lastname: Jerónimo
authors.affiliation: Cancer Biology and Epigenetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.|Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.|Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Paulo
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.|Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.|Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
mesh_terms: D058674:Chromosome Duplication; D002898:Chromosomes, Human, Pair 8; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000503:physiopathology
chemical_list: C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2