Distinct genomic aberrations associated with ERG rearranged prostate cancer.

TitleDistinct genomic aberrations associated with ERG rearranged prostate cancer.
Publication TypeJournal Article
Year of Publication2009
AuthorsDemichelis F, Setlur SR, Beroukhim R, Perner S, Korbel JO, Lafargue CJ, Pflueger D, Pina C, Hofer MD, Sboner A, Svensson MA, Rickman DS, Urban A, Snyder M, Meyerson M, Lee C, Gerstein MB, Kuefer R, Rubin MA
JournalGenes Chromosomes Cancer
Date Published2009 Apr
KeywordsCell Line, Tumor, Chromosome Aberrations, Chromosome Mapping, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Humans, In Situ Hybridization, Fluorescence, Male, Oligonucleotide Array Sequence Analysis, Prostatic Neoplasms, Proto-Oncogene Proteins c-ets, Trans-Activators

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.

Alternate JournalGenes Chromosomes Cancer
PubMed ID19156837
PubMed Central IDPMC2674964
Grant List5K08CA122833-02 / CA / NCI NIH HHS / United States
PCO40715 / / PHS HHS / United States
R01 CA116337 / CA / NCI NIH HHS / United States
R01 CA116337-03 / CA / NCI NIH HHS / United States
R01CA109038 / CA / NCI NIH HHS / United States
R01CA116337 / CA / NCI NIH HHS / United States
R01CA125612 / CA / NCI NIH HHS / United States