Novel 5′ Fusion Partners of ETV1 and ETV4 in Prostate Cancer

Gene fusions involving the erythroblast transformation-specific (ETS) transcription factors ERG, ETV1, ETV4, ETV5, and FLI1 are a common feature of prostate carcinomas (PCas). Themost common upstream fusion partner described is the androgenregulated prostate-specific gene TMPRSS2, most frequently wi...

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Main Authors: Joao D. Barros-Silva, Paula Paulo, Anne Cathrine Bakken, Nuno Cerveira, Marthe Løvf, Rui Henrique, Carmen Jerönimo, Ragnhild A. Lothe, Rolf Inge Skotheim, Manuel R. Teixeira
Format: Article
Language:English
Published: Elsevier 2013-07-01
Series:Neoplasia: An International Journal for Oncology Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1476558613800668
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author Joao D. Barros-Silva
Paula Paulo
Anne Cathrine Bakken
Nuno Cerveira
Marthe Løvf
Rui Henrique
Carmen Jerönimo
Ragnhild A. Lothe
Rolf Inge Skotheim
Manuel R. Teixeira
author_facet Joao D. Barros-Silva
Paula Paulo
Anne Cathrine Bakken
Nuno Cerveira
Marthe Løvf
Rui Henrique
Carmen Jerönimo
Ragnhild A. Lothe
Rolf Inge Skotheim
Manuel R. Teixeira
author_sort Joao D. Barros-Silva
collection DOAJ
description Gene fusions involving the erythroblast transformation-specific (ETS) transcription factors ERG, ETV1, ETV4, ETV5, and FLI1 are a common feature of prostate carcinomas (PCas). Themost common upstream fusion partner described is the androgenregulated prostate-specific gene TMPRSS2, most frequently with ERG, but additional 5′fusion partners have been described. We performed 5′ rapid amplification of cDNA ends in 18 PCas with ETV1, ETV4, or ETV5 outlier expression to identify the 5′ fusion partners. We also evaluated the exon-level expression profile of these ETS genes in 14 cases. We identified and confirmed by fluorescent in situ hybridization (FISH) and reverse transcription-polymerase chain reaction the two novel chimeric genes OR51E2-ETV1 and UBTF-ETV4 in two PCas. OR51E2 encodes a G-protein.coupled receptor that is overexpressed in PCas, whereas UBTF is a ubiquitously expressed gene encoding an HMG-box DNA-binding protein involved in ribosome biogenesis. We additionally describe two novel gene fusion combinations of previously described genes, namely, SLC45A3- ETV4 and HERVK17-ETV4. Finally, we found one PCa with TMPRSS2-ETV1, one with C15orf21-ETV1, one with EST14-ETV1, and two with 14q133-q21.1-ETV1. In nine PCas (eight ETV1 and one ETV5), exhibiting ETS outlier expression and genomic rearrangement detected by FISH, no 5′ fusion partner was found. Our findings contribute significantly to characterize the heterogeneous group of ETS gene fusions and indicate that all genes described as 5′ fusion partners with one ETS gene can most likely be rearranged with any of the other ETS genes involved in prostate carcinogenesis.
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spelling doaj.art-9078565292754abf9399e868a3bc34d72022-12-22T00:48:20ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022013-07-0115772072610.1593/neo.13232Novel 5′ Fusion Partners of ETV1 and ETV4 in Prostate CancerJoao D. Barros-Silva0Paula Paulo1Anne Cathrine Bakken2Nuno Cerveira3Marthe Løvf4Rui Henrique5Carmen Jerönimo6Ragnhild A. Lothe7Rolf Inge Skotheim8Manuel R. Teixeira9Department of Genetics, Portuguese Oncology Institute, Porto, PortugalDepartment of Genetics, Portuguese Oncology Institute, Porto, PortugalDepartment of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayDepartment of Genetics, Portuguese Oncology Institute, Porto, PortugalDepartment of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayDepartment of Pathology, Portuguese Oncology Institute, Porto, PortugalDepartment of Genetics, Portuguese Oncology Institute, Porto, PortugalDepartment of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayDepartment of Genetics, Portuguese Oncology Institute, Porto, PortugalGene fusions involving the erythroblast transformation-specific (ETS) transcription factors ERG, ETV1, ETV4, ETV5, and FLI1 are a common feature of prostate carcinomas (PCas). Themost common upstream fusion partner described is the androgenregulated prostate-specific gene TMPRSS2, most frequently with ERG, but additional 5′fusion partners have been described. We performed 5′ rapid amplification of cDNA ends in 18 PCas with ETV1, ETV4, or ETV5 outlier expression to identify the 5′ fusion partners. We also evaluated the exon-level expression profile of these ETS genes in 14 cases. We identified and confirmed by fluorescent in situ hybridization (FISH) and reverse transcription-polymerase chain reaction the two novel chimeric genes OR51E2-ETV1 and UBTF-ETV4 in two PCas. OR51E2 encodes a G-protein.coupled receptor that is overexpressed in PCas, whereas UBTF is a ubiquitously expressed gene encoding an HMG-box DNA-binding protein involved in ribosome biogenesis. We additionally describe two novel gene fusion combinations of previously described genes, namely, SLC45A3- ETV4 and HERVK17-ETV4. Finally, we found one PCa with TMPRSS2-ETV1, one with C15orf21-ETV1, one with EST14-ETV1, and two with 14q133-q21.1-ETV1. In nine PCas (eight ETV1 and one ETV5), exhibiting ETS outlier expression and genomic rearrangement detected by FISH, no 5′ fusion partner was found. Our findings contribute significantly to characterize the heterogeneous group of ETS gene fusions and indicate that all genes described as 5′ fusion partners with one ETS gene can most likely be rearranged with any of the other ETS genes involved in prostate carcinogenesis.http://www.sciencedirect.com/science/article/pii/S1476558613800668
spellingShingle Joao D. Barros-Silva
Paula Paulo
Anne Cathrine Bakken
Nuno Cerveira
Marthe Løvf
Rui Henrique
Carmen Jerönimo
Ragnhild A. Lothe
Rolf Inge Skotheim
Manuel R. Teixeira
Novel 5′ Fusion Partners of ETV1 and ETV4 in Prostate Cancer
Neoplasia: An International Journal for Oncology Research
title Novel 5′ Fusion Partners of ETV1 and ETV4 in Prostate Cancer
title_full Novel 5′ Fusion Partners of ETV1 and ETV4 in Prostate Cancer
title_fullStr Novel 5′ Fusion Partners of ETV1 and ETV4 in Prostate Cancer
title_full_unstemmed Novel 5′ Fusion Partners of ETV1 and ETV4 in Prostate Cancer
title_short Novel 5′ Fusion Partners of ETV1 and ETV4 in Prostate Cancer
title_sort novel 5 fusion partners of etv1 and etv4 in prostate cancer
url http://www.sciencedirect.com/science/article/pii/S1476558613800668
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