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Distinct genomic aberrations associated with ERG rearranged prostate cancer
Author(s) -
Demichelis Francesca,
Setlur Sunita R.,
Beroukhim Rameen,
Perner Sven,
Korbel Jan O.,
LaFargue Christopher J.,
Pflueger Dorothee,
Pina Cara,
Hofer Matthias D.,
Sboner Andrea,
Svensson Maria A.,
Rickman David S.,
Urban Alex,
Snyder Michael,
Meyerson Matthew,
Lee Charles,
Gerstein Mark B.,
Kuefer Rainer,
Rubin Mark A.
Publication year - 2009
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.20647
Subject(s) - prostate cancer , fusion gene , tmprss2 , biology , prostate , breakpoint , chromoplexy , comparative genomic hybridization , cancer research , copy number variation , copy number analysis , gene , erg , cancer , computational biology , genetics , genome , pca3 , medicine , disease , chromosomal translocation , retina , covid-19 , neuroscience , infectious disease (medical specialty)
Emerging molecular and clinical data suggest that ETS fusion prostate cancer represents a distinct molecular subclass, driven most commonly by a hormonally regulated promoter and characterized by an aggressive natural history. The study of the genomic landscape of prostate cancer in the light of ETS fusion events is required to understand the foundation of this molecularly and clinically distinct subtype. We performed genome‐wide profiling of 49 primary prostate cancers and identified 20 recurrent chromosomal copy number aberrations, mainly occurring as genomic losses. Co‐occurring events included losses at 19q13.32 and 1p22.1. We discovered three genomic events associated with ERG rearranged prostate cancer, affecting 6q, 7q, and 16q. 6q loss in nonrearranged prostate cancer is accompanied by gene expression deregulation in an independent dataset and by protein deregulation of MYO6. To analyze copy number alterations within the ETS genes, we performed a comprehensive analysis of all 27 ETS genes and of the 3 Mbp genomic area between ERG and TMPRSS2 (21q) with an unprecedented resolution (30 bp). We demonstrate that high‐resolution tiling arrays can be used to pin‐point breakpoints leading to fusion events. This study provides further support to define a distinct molecular subtype of prostate cancer based on the presence of ETS gene rearrangements. © 2009 Wiley‐Liss,Inc.