ETS fusion genes in prostate cancer

Abstract

Prostate cancer is very common in elderly men in developed countries. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. ERG is an oncogene that encodes a member of the family of ETS transcription factors. At lower frequency, other members of this gene family are also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen-regulated gene that is preferentially expressed in the prostate. Most of the less frequent ETS fusion partners are also androgen-regulated and prostatespecific. During the last few years, novel concepts of the process of gene fusion have emerged, and initial experimental results explaining the function of the ETS genes ERG and ETV1 in prostate cancer have been published. In this review, we focus on the most relevant ETS gene fusions and summarize the current knowledge of the role of ETS transcription factors in prostate cancer. Finally, we discuss the clinical relevance of TMRPSS2-ERG and other ETS gene fusions in prostate cancer.

Metabolomic profiling for the identification of novel diagnostic markers in prostate cancer

“…Because early diagnosis improves treatment efficacy and the quality of life, as well as reducing the cost for disease management, new biomarkers have been evaluated to increase the sensitivity and specificity for PCa diagnosis and prognosis, and reduce the number of unnecessary biopsies. These biomarkers include Prostate Cancer Antigen 3 (PCA3), the TMPRSS2-ERG gene fusion, Spondin 2, and circulating tumor cells [4][5][6][7][8][9][10].…”

“…Moreover, a persistent activation of the AR signaling and chromosomal rearrangements that result in a high level expression of ETS gene family members (ERG, ETV1) have been shown to be common events in PCa progression [6,[75][76][77][78]. Chromatin immunoprecipitation sequencing revealed a direct binding of the AR and ERG to the GNMT promoter, while knockdown of TMPRSS2-ERG gene fusion in the VCaP cell line resulted in a decrease of sarcosine levels.…”

Determinants of Receptor- and Tissue-Specific Actions in Androgen Signaling

“…Thus far, FOXA1 is the bestcharacterized pioneer factor in the context of both breast and prostate cancer (214). In prostate cancer, ETS family members have also special interest due to their involvement in recurrent TMPRSS2-driven fusion genes (74,144), although their function in prostate cancer is not yet fully understood (215). Furthermore, several collaborating factors bind in many cases to shared loci together with AR and ER, such as FOXA1 and GATA-2 in prostate cancer cells and FOXA1 and GATA-3 in breast cancer cells, respectively (166,167), but their functional interplay in specific steroid receptor binding needs further characterization.…”

Novel TNS3-MAP3K3 and ZFPM2-ELF5 fusion genes identified by RNA sequencing in multicystic mesothelioma with t(7;17)(p12;q23) and t(8;11)(q23;p13)

“…Several ETS transcription factors have been associated with cancer initiation, progression, and metastasis, the paradigmatic example being the fusion of FLI1 with EWSR1 in Ewing sarcoma with t(11;22) which generates a chimeric EWSR1-FLI1 transcription factor [22]. Worthy of note is also that members of the ETS family of transcription factors -ERG, ETV1 etcetera -are overexpressed in prostate carcinoma as a result of their fusion with the TMPRSS2 gene [34].…”