title: Two unique novel prostate-specific and androgen-regulated fusion partners of ETV4 in prostate cancer.
abstract: Recently, fusion of ERG to the androgen-regulated, prostate-specific TMPRSS2 gene has been identified as the most frequent genetic alteration in prostate cancer. At low frequency, TMPRSS2-ETV1 and TMPRSS2-ETV4 fusion genes have been described. In this study, we report two novel ETV4 fusion genes in prostate cancer: KLK2-ETV4 and CANT1-ETV4. Both gene fusions have important unique aspects. KLK2 is a well-established androgen-induced and prostate-specific gene. Fusion of KLK2 to ETV4 results in the generation of an additional ETV4 exon, denoted exon 4a. This novel exon delivers an ATG for the longest open reading frame, in this way avoiding translation start in KLK2 exon 1. Although wild-type CANT1 has two alternative first exons (exons 1 and 1a), only exon 1a was detected in CANT1-ETV4 fusion transcripts. We show that CANT1 transcripts starting at exon 1a have an androgen-induced and prostate-specific expression pattern, whereas CANT1 transcripts starting at exon 1 are not prostate specific. So, the two novel ETV4 fusion partners possess as predominant common characteristics androgen-induction and prostate-specific expression.
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Karin G
authors.initials: KG
authors.lastname: Hermans
authors.forename: Anke A
authors.initials: AA
authors.lastname: Bressers
authors.forename: Hetty A
authors.initials: HA
authors.lastname: van der Korput
authors.forename: Natasja F
authors.initials: NF
authors.lastname: Dits
authors.forename: Guido
authors.initials: G
authors.lastname: Jenster
authors.forename: Jan
authors.initials: J
authors.lastname: Trapman
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000378:metabolism; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics; D009708:Nucleotidases / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D014018:Tissue Distribution; D020840:Tissue Kallikreins / Q000235:genetics / Q000378:metabolism
chemical_list: D017500:Adenovirus E1A Proteins; D000728:Androgens; C079853:ETV4 protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D009708:Nucleotidases; D020840:Tissue Kallikreins; C526909:calcium-activated nucleotidase, human