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

摘要

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.