ERG rearrangement is specific to prostate cancer and does not occur in any other common tumor.
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.
Scheble
Veit J
VJ
Institute of Pathology, Comprehensive Cancer Center, University Hospital of Tuebingen, Tuebingen, Germany.
Braun
Martin
M
Beroukhim
Rameen
R
Mermel
Craig H
CH
Ruiz
Christian
C
Wilbertz
Theresia
T
Stiedl
Ann-Cathrin
AC
Petersen
Karen
K
Reischl
Markus
M
Kuefer
Rainer
R
Schilling
David
D
Fend
Falko
F
Kristiansen
Glen
G
Meyerson
Matthew
M
Rubin
Mark A
MA
Bubendorf
Lukas
L
Perner
Sven
S
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
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
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