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NCOA2 is a candidate target gene of 8q gain associated with clinically aggressive prostate cancer
Author(s) -
Silva Maria P.,
BarrosSilva João D.,
Vieira Joana,
Lisboa Susana,
Torres Lurdes,
Correia Cecília,
VieiraCoimbra Márcia,
Martins Ana T.,
Jerónimo Carmen,
Henrique Rui,
Paulo Paula,
Teixeira Manuel R.
Publication year - 2016
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22340
Subject(s) - prostate cancer , biology , tmprss2 , gene , cancer research , erg , fluorescence in situ hybridization , tissue microarray , fusion gene , cancer , oncology , medicine , genetics , retina , disease , covid-19 , neuroscience , infectious disease (medical specialty) , chromosome
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. © 2016 Wiley Periodicals, Inc.