Distinct genomic aberrations associated with ERG rearranged prostate cancer.
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.
Demichelis
Francesca
F
Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY 10065.
Setlur
Sunita R
SR
Beroukhim
Rameen
R
Perner
Sven
S
Korbel
Jan O
JO
Lafargue
Christopher J
CJ
Pflueger
Dorothee
D
Pina
Cara
C
Hofer
Matthias D
MD
Sboner
Andrea
A
Svensson
Maria A
MA
Rickman
David S
DS
Urban
Alex
A
Snyder
Michael
M
Meyerson
Matthew
M
Lee
Charles
C
Gerstein
Mark B
MB
Kuefer
Rainer
R
Rubin
Mark A
MA
D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
C072312:ERG protein, human; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG