Structure and Function of the Splice Variants of TMPRSS2-ERG, a Prevalent Genomic Alteration in Prostate Cancer

摘要

The most common early genetic defect in prostate cancer (CaP) is the TMPRSS2-ERG gene fusion that results in the expression of the ERG protooncogene. In the context of rearranged genome ERG is transcribed under the control of the androgen inducible TMPRSS2 promoter producing cancer-associated splice variants of ERG. Although, much has been learned in recent years about gene fusions in prostate cancer, the function of TMPRSS2-ERG splice variants is not well understood. However, this information is critical in order to understand ERG functions and its therapeutic targeting in CaP. We have identified two major classes of full-length transcripts of ERG, Type I and Type II splice variants, by screening a cDNA library of TMPRSS2-ERG fusion harboring human prostate tumors. Type I over Type II increased ratios correlated with poor prognostic and clinico-pathologic features of CaP. Moreover, we have found the dominant presence of Type II form in prostate cancer cells. Functional interaction between Type II and Type I splice variants in prostate tumor cells is currently under investigation. Expression of ERG splice variants in human CaP, and the relative ratio of splice variants may provide new strategy in prognosing prostate cancer.