title: Distinct genomic aberrations associated with ERG rearranged prostate cancer.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY 10065.
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
authors.forename: Sunita R
authors.initials: SR
authors.lastname: Setlur
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Jan O
authors.initials: JO
authors.lastname: Korbel
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lafargue
authors.forename: Dorothee
authors.initials: D
authors.lastname: Pflueger
authors.forename: Cara
authors.initials: C
authors.lastname: Pina
authors.forename: Matthias D
authors.initials: MD
authors.lastname: Hofer
authors.forename: Andrea
authors.initials: A
authors.lastname: Sboner
authors.forename: Maria A
authors.initials: MA
authors.lastname: Svensson
authors.forename: David S
authors.initials: DS
authors.lastname: Rickman
authors.forename: Alex
authors.initials: A
authors.lastname: Urban
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
authors.forename: Rainer
authors.initials: R
authors.lastname: Kuefer
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: 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
chemical_list: C072312:ERG protein, human; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG