N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate Cancer
A step toward the molecular classification of prostate cancer was the discovery of recurrent erythroblast transformation. specific rearrangements, most commonly fusing the androgen-regulated TMPRSS2 promoter to ERG. The TMPRSS2-ERG fusion is observed in around 90% of tumors that overexpress the onco...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2009-08-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S147655860980136X |
| _version_ | 1830077561961447424 |
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| author | Dorothee Pflueger David S. Rickman Andrea Sboner Sven Perner Christopher J. LaFargue Maria A. Svensson Benjamin J. Moss Naoki Kitabayashi Yihang Pan Alexandre de la Taille Rainer Kuefer Ashutosh K. Tewari Francesca Demichelis Mark S. Chee Mark B. Gerstein Mark A. Rubin |
| author_facet | Dorothee Pflueger David S. Rickman Andrea Sboner Sven Perner Christopher J. LaFargue Maria A. Svensson Benjamin J. Moss Naoki Kitabayashi Yihang Pan Alexandre de la Taille Rainer Kuefer Ashutosh K. Tewari Francesca Demichelis Mark S. Chee Mark B. Gerstein Mark A. Rubin |
| author_sort | Dorothee Pflueger |
| collection | DOAJ |
| description | A step toward the molecular classification of prostate cancer was the discovery of recurrent erythroblast transformation. specific rearrangements, most commonly fusing the androgen-regulated TMPRSS2 promoter to ERG. The TMPRSS2-ERG fusion is observed in around 90% of tumors that overexpress the oncogene ERG. The goal of the current study was to complete the characterization of these ERG-overexpressing prostate cancers. Using fluorescence in situ hybridization and reverse transcription.polymerase chain reaction assays, we screened 101 prostate cancers, identifying 34 cases (34%) with the TMPRSS2-ERG fusion. Seven cases demonstrated ERG rearrangement by fluorescence in situ hybridization without the presence of TMPRSS2-ERG fusion messenger RNA transcripts. Screening for known 5' partners, we determined that three cases harbored the SLC45A3-ERG fusion. To discover novel 5' partners in these ERG-overexpressing and ERG-rearranged cases, we used paired-end RNA sequencing. We first confirmed the utility of this approach by identifying the TMPRSS2-ERG fusion in a known positive prostate cancer case and then discovered a novel fusion involving the androgen-inducible tumor suppressor, NDRG1 (N-myc downstream regulated gene 1), and ERG in two cases. Unlike TMPRSS2-ERG and SCL45A3-ERG fusions, the NDRG1-ERG fusion is predicted to encode a chimeric protein. Like TMPRSS2, SCL45A3 and NDRG1 are inducible not only by androgen but also by estrogen. This study demonstrates that most ERG-overexpressing prostate cancers harbor hormonally regulated TMPRSS2-ERG, SLC45A3-ERG, or NDRG1-ERG fusions. Broader implications of this study support the use of RNA sequencing to discover novel cancer translocations. |
| first_indexed | 2024-12-13T17:19:21Z |
| format | Article |
| id | doaj.art-ab06c41d234641e7a4cb0a3122e76019 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-13T17:19:21Z |
| publishDate | 2009-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-ab06c41d234641e7a4cb0a3122e760192022-12-21T23:37:21ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022009-08-0111880481110.1593/neo.09572N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate CancerDorothee Pflueger0David S. Rickman1Andrea Sboner2Sven Perner3Christopher J. LaFargue4Maria A. Svensson5Benjamin J. Moss6Naoki Kitabayashi7Yihang Pan8Alexandre de la Taille9Rainer Kuefer10Ashutosh K. Tewari11Francesca Demichelis12Mark S. Chee13Mark B. Gerstein14Mark A. Rubin15Department of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USADepartment of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USAINSERM, Unité 955, Créteil, FranceDepartment of Urology, University Hospital Ulm, Ulm, GermanyDepartment of Urology, Weill Cornell Medical College, New York, NY, USADepartment of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USAPrognosys Biosciences Inc., La Jolla, CA, USADepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USADepartment of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USAA step toward the molecular classification of prostate cancer was the discovery of recurrent erythroblast transformation. specific rearrangements, most commonly fusing the androgen-regulated TMPRSS2 promoter to ERG. The TMPRSS2-ERG fusion is observed in around 90% of tumors that overexpress the oncogene ERG. The goal of the current study was to complete the characterization of these ERG-overexpressing prostate cancers. Using fluorescence in situ hybridization and reverse transcription.polymerase chain reaction assays, we screened 101 prostate cancers, identifying 34 cases (34%) with the TMPRSS2-ERG fusion. Seven cases demonstrated ERG rearrangement by fluorescence in situ hybridization without the presence of TMPRSS2-ERG fusion messenger RNA transcripts. Screening for known 5' partners, we determined that three cases harbored the SLC45A3-ERG fusion. To discover novel 5' partners in these ERG-overexpressing and ERG-rearranged cases, we used paired-end RNA sequencing. We first confirmed the utility of this approach by identifying the TMPRSS2-ERG fusion in a known positive prostate cancer case and then discovered a novel fusion involving the androgen-inducible tumor suppressor, NDRG1 (N-myc downstream regulated gene 1), and ERG in two cases. Unlike TMPRSS2-ERG and SCL45A3-ERG fusions, the NDRG1-ERG fusion is predicted to encode a chimeric protein. Like TMPRSS2, SCL45A3 and NDRG1 are inducible not only by androgen but also by estrogen. This study demonstrates that most ERG-overexpressing prostate cancers harbor hormonally regulated TMPRSS2-ERG, SLC45A3-ERG, or NDRG1-ERG fusions. Broader implications of this study support the use of RNA sequencing to discover novel cancer translocations.http://www.sciencedirect.com/science/article/pii/S147655860980136X |
| spellingShingle | Dorothee Pflueger David S. Rickman Andrea Sboner Sven Perner Christopher J. LaFargue Maria A. Svensson Benjamin J. Moss Naoki Kitabayashi Yihang Pan Alexandre de la Taille Rainer Kuefer Ashutosh K. Tewari Francesca Demichelis Mark S. Chee Mark B. Gerstein Mark A. Rubin N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate Cancer Neoplasia: An International Journal for Oncology Research |
| title | N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate Cancer |
| title_full | N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate Cancer |
| title_fullStr | N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate Cancer |
| title_full_unstemmed | N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate Cancer |
| title_short | N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate Cancer |
| title_sort | n myc downstream regulated gene 1 ndrg1 is fused to erg in prostate cancer |
| url | http://www.sciencedirect.com/science/article/pii/S147655860980136X |
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