Androgen Regulation of ETS Gene Fusion Transcripts in Prostate Cancer

Abstract

Fusion between androgen-regulated TMPRSS2 and ETS transcription factor gene ERG is the most frequent genetic alteration that occurs in 40–70% of prostate cancers. Not only ERG but also other ETS transcription factor genes are involved in gene fusions. ETV1, ETV4, and ETV5 have all several fusion partners. One common feature shared by the majority of these partners is androgen-regulated expression. Despite its high frequency, the biological and molecular effects of ETS gene fusion in prostate cancer development and progression are unknown. In this chapter quantitative polymerase chain reaction (Q-PCR) is used for detection and further studying the incidence and properties of these fusion transcripts. The focus is on the expression of TMPRSS2–ERG transcripts in clinical prostate samples. Androgen regulation of TMPRSS2 is measured in commonly used LNCaP prostate cancer cells grown with and without the synthetic androgen R1881. Furthermore, combining Q-PCR with 5′ RLM-RACE and sequencing are described for the identification of novel ETS fusion partners.