Recurrent Fusion of <i>TMPRSS2</i> and ETS Transcription Factor Genes in Prostate Cancer

TLDR

Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations based on outlier gene expression. We combined a bioinformatics screen of outlier expression with cell‑line experiments showing that androgen‑responsive promoter elements of TMPRSS2 drive overexpression of ETS family members. We identified ERG and ETV1 as outlier ETS transcription factors, found recurrent TMPRSS2‑ERG or TMPRSS2‑ETV1 fusions in prostate cancer tissues, observed rearrangements in 23 of 29 samples by FISH, and highlighted implications for carcinogenesis and molecular diagnosis and treatment.

Abstract

Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression. Two ETS transcription factors, ERG and ETV1, were identified as outliers in prostate cancer. We identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlier expression. By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1. Cell line experiments suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members in prostate cancer. These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer.