title: Concurrent TMPRSS2-ERG and SLC45A3-ERG rearrangements plus PTEN loss are not found in low grade prostate cancer and define an aggressive tumor subset.
abstract: SLC45A3 is the second most common ERG partner in prostate cancer (PrCa). Coexisting TMPRSS2 and SLC45A3 rearrangements are found in a subset of cases, but the meaning is still unknown.
  
  
  
  SLC45A3-ERG and TMPRSS2-ERG rearrangements and their association with ERG and PTEN expression and with clinical and pathological features have been analyzed in 80 PrCa (PSMAR-Biobank, Barcelona, Spain). ERG and PTEN mRNA were assessed by qRT-PCR; TMPRSS2-ERG and SLC45A3-ERG by RT-PCR, FISH, and direct sequencing; and ERG expression by IHC. The endpoints were Gleason score (GS), stage, and PSA progression-free survival.
  
  
  
  Single TMPRSS2-ERG was found in 51.6% GS ≤ 7 and 22.2% GS ≥ 8 tumors (P = 0.027). SLC45A3-ERG was found in 25 cases, 20 of them with concurrent TMPRSS2-ERG rearrangement: 11.5% GS = 6, 22.2% GS = 7, and 50% GS ≥ 8 tumors (P = 0.013). Double rearrangements were associated with higher levels of ERG mRNA (P = 0.04). Double rearrangement plus PTEN loss was detected in 0% GS = 6; 14.7% GS = 7, and 29.4% GS ≥ 8 tumors (P = 0.032). Furthermore, this triple change was present in 19.2% stage T3-4 but not in any of stage T2 tumors (P = 0.05). No relationship was found with PSA progression-free survival.
  
  
  
  Single TMPRSS2-ERG translocation is associated with low grade PrCa. Subsequent development of SLC45A3-ERG results in higher ERG expression. The combination of double rearrangement plus PTEN loss, according to our series, is never found in low grade, low stage tumors. These findings could be potentially useful in therapeutic decision making in PrCa. Tumors with combined TMPRSS2-ERG/SLC45A3-ERG fusions plus PTEN loss should be excluded from watchful waiting and are candidates for intensive therapy. Prostate 76:854-865, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Hernández
authors.affiliation: Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Font-Tello
authors.affiliation: Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.|Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Juanpere
authors.affiliation: Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: de Muga
authors.affiliation: Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Lorenzo
authors.affiliation: Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Salido
authors.affiliation: Department of Urology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Fumadó
authors.affiliation: Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Serrano
authors.affiliation: Department of Urology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Cecchini
authors.affiliation: Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.|Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Serrano
authors.affiliation: Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.|Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
mesh_terms: D018572:Disease-Free Survival; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009004:Monosaccharide Transport Proteins; D060787:Neoplasm Grading; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071230:Transcriptional Regulator ERG / Q000235:genetics / Q000378:metabolism
chemical_list: C072312:ERG protein, human; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; D015514:Oncogene Proteins, Fusion; C551031:SLC45a3 protein, human; C515553:TMPRSS2-ERG fusion protein, human; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: PTEN; SLC45A3-ERG; TMPRSS2-ERG; prostate cancer