High‐resolution ERG‐expression profiling on GeneChip exon 1.0 ST arrays in primary and castration‐resistant prostate cancer

• Published in: BJU international Vol. 111; no. 5; pp. 836 - 842
• Main Authors: Smit, Frank P., Salagierski, Maciej, Jannink, Sander, Schalken, Jack A.
• Format: Journal Article
• Language: English
• Published: Oxford Wiley-Blackwell 01-05-2013; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Biological and medical sciences; diagnosis; ERG; Exons; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Oligonucleotide Array Sequence Analysis; Oncogene Fusion; Oncogene Proteins, Fusion; Orchiectomy; Prostate - metabolism; Prostate - pathology; prostate cancer; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - surgery; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm - genetics; TMPRSS2‐ERG fusions; Trans-Activators - biosynthesis; Trans-Activators - genetics; Transcriptional Regulator ERG; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; High resolution; Nephrology; Urinary system disease; Prostate disease; Malignant tumor; Urology; Gene expression profile; Resistance; Exon; Castration; C-Onc gene; Diagnosis; ERG; TMPRSS2-ERG fusions; Male genital diseases; Prostate cancer; Protooncogene; Cancer; Primary cancer
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/bju.12119

Objective
To assess whether oestrogen‐regulated gene (ERG) expression analysis using GeneChip arrays can predict transmembrane protease, serine 2 (TMPRSS2)‐ERG fusion. The expression level of the TMPRSS2‐ERG gene was studied in various histological grades of prostate cancer and castration‐resistant prostate cancer (CPRC).
Patients and methods
GeneChip Affymetrix exon 1.0 ST arrays were used for expression profiling of ERG, erythroblast transformation‐specific (ETS) variant gene 1 (ETV1), ETV4 and ETV5 genes in 67 prostate cancer tissue specimens.
Real‐time quantitative polymerase chain reaction analysis and in some cases DNA sequencing was used to validate the presence and the expression levels of TMPRSS2‐ERG gene fusions.
Results
In our series of patients with prostate cancer over expression of the ERG gene predicted the presence of TMPRSS2‐ERG rearrangements in almost all cases. ETS expression by itself outmatched the diagnostic performance of the ERG exons ratioing allowing equal detection of the less frequent ETS gene fusion transcripts.
The gene fusions were expressed at significantly lower levels in CPRC but occurred more frequently than in primary prostate cancer.
Conclusions
ERG expression analysis using GeneChip arrays appears to be an excellent diagnostic tool for identifying gene rearrangements.
In coming years, measuring expression of the ETS gene family by itself might become a clinically relevant surrogate test to identify patients with fusion‐positive prostate cancer.
The variation of gene fusion expression levels, particularly in CPRC, needs to be taken into account when using quantitative molecular diagnosis of prostate cancer.