Noninvasive detection of TMPRSS2:ERG fusion transcripts in the urine of men with prostate cancer.
We recently reported the identification of recurrent gene fusions in the majority of prostate cancers involving the 5' untranslated region of the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, and ETV4. Here we report the noninvasive detection of these gene fusions in the urine of patients with clinically localized prostate cancer. By quantitative polymerase chain reaction, we assessed the expression of ERG and TMPRSS2:ERG transcripts in urine samples obtained after prostatic massage from 19 patients (11 prebiopsy and 8 pre-radical prostatectomy) with prostate cancer. We observed a strong concordance between ERG overexpression and TMPRSS2:ERG expression, with 8 of 19 (42%) patients having detectable TMPRSS2:ERG transcripts in their urine. Importantly, by fluorescence in situ hybridization, we confirmed the presence or the absence of TMPRSS2:ERG gene fusions in matched prostate cancer tissue samples from three of three patients with fusion transcripts in their urine and from two of two patients without fusion transcripts in their urine. These results demonstrate that TMPRSS2:ERG gene fusions can be detected in the urine of patients with prostate cancer and support larger studies on prospective cohorts for noninvasive detection of prostate cancer.
Laxman
Bharathi
B
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Tomlins
Scott A
SA
Mehra
Rohit
R
Morris
David S
DS
Wang
Lei
L
Helgeson
Beth E
BE
Shah
Rajal B
RB
Rubin
Mark A
MA
Wei
John T
JT
Chinnaiyan
Arul M
AM
D020121:5' Untranslated Regions / Q000235:genetics; D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics / Q000652:urine*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005240:Feasibility Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000652:urine*; D012333:RNA, Messenger / Q000235:genetics / Q000652:urine*; D012334:RNA, Neoplasm / Q000235:genetics / Q000652:urine*; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
D020121:5' Untranslated Regions; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human; D017430:Prostate-Specific Antigen