title: ERG rearrangement is specific to prostate cancer and does not occur in any other common tumor.
abstract: Identification of specific somatic gene alterations is crucial for the insight into the development, progression, and clinical behavior of individual cancer types. The recently discovered recurrent ERG rearrangement in prostate cancer might represent a prostate cancer-specific alteration that has not been systematically assessed in tumors other than prostate cancer. Aim of this study was to assess, whether the ERG rearrangement and the distinct deletion site between TMPRSS2 and ERG, both predominantly resulting in a TMPRSS2-ERG fusion, occur in tumors other than prostate cancer. We assessed 54 different tumor types (2942 samples in total) for their ERG rearrangement status by fluorescence in situ hybridization (FISH). To calibrate, we analyzed 285 prostate cancer samples for the ERG rearrangement frequency. Additionally, we interrogated a high-resolution single nucleotide polymorphism (SNP) data set across 3131 cancer specimens (26 tumor types) for copy number alterations. None of the 54 different tumor types assessed by FISH harbored an ERG rearrangement, whereas the prostate cancer samples revealed an ERG rearrangement in 49.5% of cases. Furthermore, within the 26 tumor types assessed for copy number alterations by SNP, the distinct deletion site between TMPRSS2 and ERG (21q22.2-3) was detectable exclusively in prostate cancer. Although Ewing's sarcoma and AML have known rearrangements rarely involving ERG, we hypothesize that the ERG rearrangement as well as the distinct deletion site on 21q22.2-3 between TMPRSS2 and ERG are prostate-cancer-specific genomic alterations. These observations provide further insight into the oncogenesis of prostate cancer and might be critical for the development of ERG rearrangement assessment as a clinical tool.
authors.affiliation: Institute of Pathology, Comprehensive Cancer Center, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Veit J
authors.initials: VJ
authors.lastname: Scheble
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.forename: Craig H
authors.initials: CH
authors.lastname: Mermel
authors.forename: Christian
authors.initials: C
authors.lastname: Ruiz
authors.forename: Theresia
authors.initials: T
authors.lastname: Wilbertz
authors.forename: Ann-Cathrin
authors.initials: AC
authors.lastname: Stiedl
authors.forename: Karen
authors.initials: K
authors.lastname: Petersen
authors.forename: Markus
authors.initials: M
authors.lastname: Reischl
authors.forename: Rainer
authors.initials: R
authors.lastname: Kuefer
authors.forename: David
authors.initials: D
authors.lastname: Schilling
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015514:Oncogene Proteins, Fusion; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D012697:Serine Endopeptidases; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: D004273:DNA, Neoplasm; C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
references.citation: Histopathology. 2010 Jun;56(7):937-43
references.pmid: 20636794
references.citation: Cancer Res. 2006 Sep 1;66(17):8337-41
references.pmid: 16951139
references.citation: Clin Cancer Res. 2009 Jul 15;15(14):4706-11
references.pmid: 19584163
references.citation: Eur Urol. 2009 Aug;56(2):275-86
references.pmid: 19409690
references.citation: Oncogene. 2008 Sep 11;27(40):5348-53
references.pmid: 18542058
references.citation: Nature. 2010 Feb 18;463(7283):899-905
references.pmid: 20164920
references.citation: Neoplasia. 2006 Jun;8(6):465-9
references.pmid: 16820092
references.citation: Br J Cancer. 2007 Dec 17;97(12):1690-5
references.pmid: 17971772
references.citation: Cancer Res. 2006 Nov 1;66(21):10242-6
references.pmid: 17079440
references.citation: Science. 2005 Oct 28;310(5748):644-8
references.pmid: 16254181
references.citation: Genes Chromosomes Cancer. 2006 Jul;45(7):717-9
references.pmid: 16575875
references.citation: Science. 2009 Oct 9;326(5950):289-93
references.pmid: 19815776
references.citation: Neoplasia. 2008 Mar;10(3):298-302
references.pmid: 18320074
references.citation: Genes Chromosomes Cancer. 2006 Nov;45(11):1018-32
references.pmid: 16897747
references.citation: Crit Rev Oncog. 2006 Dec;12(3-4):257-71
references.pmid: 17425505
references.citation: Cancer Res. 2007 Sep 1;67(17):7991-5
references.pmid: 17804708
references.citation: Expert Rev Anticancer Ther. 2008 Oct;8(10):1675-87
references.pmid: 18925858
references.citation: Cancer Res. 2006 Sep 1;66(17):8347-51
references.pmid: 16951141
references.citation: Am J Surg Pathol. 2007 Jun;31(6):882-8
references.pmid: 17527075
references.citation: Science. 2009 Nov 27;326(5957):1230
references.pmid: 19933109
references.citation: Oncogene. 2008 Mar 27;27(14):1993-2003
references.pmid: 17922029
references.citation: Genes Chromosomes Cancer. 2005 Sep;44(1):103-8
references.pmid: 15887243
references.citation: Nat Rev Urol. 2009 Aug;6(8):429-39
references.pmid: 19657377
references.citation: Nat Rev Cancer. 2008 Jul;8(7):497-511
references.pmid: 18563191
references.citation: Nat Rev Cancer. 2007 Apr;7(4):233-45
references.pmid: 17361217
references.citation: Cancer Res. 2008 Oct 15;68(20):8516-24
references.pmid: 18922926
references.citation: Neoplasia. 2006 Oct;8(10):826-32
references.pmid: 17032499