Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA312383 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Common epithelial cancers are believed to become more aggressive through the accumulation of multiple independent molecular events that lead to the deregulation of cell signaling. However, the discovery that the majority of prostate cancers harbor gene fusions of the 5'-untranslated region of androgen regulated TMPRSS2 promoter with ETS transcription factor family members has brought this paradigm into question1,2. TMPRSS2-ERG gene fusion is the most common molecular sub-type of prostate cancer. Recent work suggests that the TMPRSS2-ERG fusion is associated with a more aggressive clinical phenotype3. In the most advanced castration resistant prostate cancers where the androgen receptor has been inactivated, the TMPRSS2-ERG fusion remains functionally active. Here we show compelling clinical and gene expression data supporting the existence of a TMPRSS2-ERG fusion prostate cancer subclass. Using expression array profiling on 455 primary prostate tumors, we identified an 87 gene expression signature, distinguishing TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity. Computational analysis suggested that this fusion signature was associated with estrogen receptor signaling. Functional studies demonstrated regulation of the TMPRSS2-ERG fusion transcript by estrogenic compounds. These data identify a previously unrecognized mechanism for regulation of the TMPRSS2-ERG, even in the absence of a functional androgen receptor, and thus may have broader implications in the treatment of prostate cancer. Keywords: Prostate cancer, Expression array, Illumina, gene fusion, TMPRSS2, ERG, Signatures, Estrogen Test Cohort: 388 cases from the population based Swedish-Watchful Waiting cohort. The cohort consists of men with localized prostate cancer (clinical stage T1-T2, Mx, N0); Validation cohort: The PhysiciansM-bM-^@M-^Y Health Study (PHS) cohort included 116 US men diagnosed with incidental prostate cancer between 1983 and 2003; 455 cases were annotated for TMPRSS2-ERG fusion. Test Set: GSM208029 ... GSM208392 Validation Set: GSM208404 ... GSM208512
2008-05-27 | E-GEOD-8402 | biostudies-arrayexpress
Project description:Common epithelial cancers are believed to become more aggressive through the accumulation of multiple independent molecular events that lead to the deregulation of cell signaling. However, the discovery that the majority of prostate cancers harbor gene fusions of the 5'-untranslated region of androgen regulated TMPRSS2 promoter with ETS transcription factor family members has brought this paradigm into question1,2. TMPRSS2-ERG gene fusion is the most common molecular sub-type of prostate cancer. Recent work suggests that the TMPRSS2-ERG fusion is associated with a more aggressive clinical phenotype3. In the most advanced castration resistant prostate cancers where the androgen receptor has been inactivated, the TMPRSS2-ERG fusion remains functionally active. Here we show compelling clinical and gene expression data supporting the existence of a TMPRSS2-ERG fusion prostate cancer subclass. Using expression array profiling on 455 primary prostate tumors, we identified an 87 gene expression signature, distinguishing TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity. Computational analysis suggested that this fusion signature was associated with estrogen receptor signaling. Functional studies demonstrated regulation of the TMPRSS2-ERG fusion transcript by estrogenic compounds. These data identify a previously unrecognized mechanism for regulation of the TMPRSS2-ERG, even in the absence of a functional androgen receptor, and thus may have broader implications in the treatment of prostate cancer. Keywords: Prostate cancer, Expression array, Illumina, gene fusion, TMPRSS2, ERG, Signatures, Estrogen
2008-05-28 | GSE8402 | GEO
Project description:TMPRSS2-ERG fusion is the most common genetic alteration in prostate cancer (PCa) and TP53 is the most frequently mutated gene in human cancers. However, their precise roles in PCa pathogenesis remain elusive. Here we showed that TMPRSS2-ERG fusion co-occurred with TP53 deletion/mutation in PCa patient specimens. ERG overexpression and Trp53 knockout/R172H mutant knockin induced pyrimidine synthesis gene (PSG) expression and prostate tumorigenesis in mice. Gain-of-function p53 mutants bound to the CTNNB1 promoter and upregulated β-Catenin. Overexpressed ERG and β-Catenin co-occupied PSG loci and mediated PSG expression, and high PSG expression associated with increased β-Catenin level and poor overall survival of PCa patients. β-Catenin inhibition by proteolysis-targeting chimeras (PROTACs) of its co-activator CBP and partner proteins LEF1/TCFs blocked ERG/p53-mutant PCa growth. Our study identifies CTNNB1 as a transcriptional target of p53 GOF-mutants, and reveals a druggable dependency on β-Catenin and pyrimidine synthesis in p53-mutated cancers with or without TMPRSS2-ERG fusion.
2023-06-27 | GSE184624 | GEO
Project description:TMPRSS2-ERG fusion is the most common genetic alteration in prostate cancer (PCa) and TP53 is the most frequently mutated gene in human cancers. However, their precise roles in PCa pathogenesis remain elusive. Here we showed that TMPRSS2-ERG fusion co-occurred with TP53 deletion/mutation in PCa patient specimens. ERG overexpression and Trp53 knockout/R172H mutant knockin induced pyrimidine synthesis gene (PSG) expression and prostate tumorigenesis in mice. Gain-of-function p53 mutants bound to the CTNNB1 promoter and upregulated β-Catenin. Overexpressed ERG and β-Catenin co-occupied PSG loci and mediated PSG expression, and high PSG expression associated with increased β-Catenin level and poor overall survival of PCa patients. β-Catenin inhibition by proteolysis-targeting chimeras (PROTACs) of its co-activator CBP and partner proteins LEF1/TCFs blocked ERG/p53-mutant PCa growth. Our study identifies CTNNB1 as a transcriptional target of p53 GOF-mutants, and reveals a druggable dependency on β-Catenin and pyrimidine synthesis in p53-mutated cancers with or without TMPRSS2-ERG fusion.
2023-06-27 | GSE184625 | GEO
Project description:TMPRSS2-ERG fusion is the most common genetic alteration in prostate cancer (PCa) and TP53 is the most frequently mutated gene in human cancers. However, their precise roles in PCa pathogenesis remain elusive. Here we showed that TMPRSS2-ERG fusion co-occurred with TP53 deletion/mutation in PCa patient specimens. ERG overexpression and Trp53 knockout/R172H mutant knockin induced pyrimidine synthesis gene (PSG) expression and prostate tumorigenesis in mice. Gain-of-function p53 mutants bound to the CTNNB1 promoter and upregulated β-Catenin. Overexpressed ERG and β-Catenin co-occupied PSG loci and mediated PSG expression, and high PSG expression associated with increased β-Catenin level and poor overall survival of PCa patients. β-Catenin inhibition by proteolysis-targeting chimeras (PROTACs) of its co-activator CBP and partner proteins LEF1/TCFs blocked ERG/p53-mutant PCa growth. Our study identifies CTNNB1 as a transcriptional target of p53 GOF-mutants, and reveals a druggable dependency on β-Catenin and pyrimidine synthesis in p53-mutated cancers with or without TMPRSS2-ERG fusion.
2023-06-27 | GSE184623 | GEO
Project description:Prostate tumors with the gene fusion TMPRSS2:ERG have been reported to have a significantly higher risk of recurrence compared with tumors lacking the fusion. Tumors from 139 patients who underwent radical prostatectomy were analyzed for the expression of 502 cancer-related genes to identify genes differentially regulated in TMPRSS2:ERG fusion tumors as well as identify biomarkers of biochemical recurrence. 139 prostate fresh-frozen tumors from radical prostatectomy surgery where profiled on the Illumina Human Cancer DASL Panel. 69 tumors were positive for the gene fusion TMPRSS2:ERG while 70 where not. 33 of the 139 patients experienced biochemical recurrence. Data was analyzed for differential genes in TMPRSS2:ERG fusion positive tumors as well as clinical and molecular biomarkers of recurrence.
2009-10-22 | E-GEOD-18655 | biostudies-arrayexpress
Project description:Antineoplastic effects of siRNA against TMPRSS2-ERG junction oncogene in prostate cancer: from molecular and cellular studies to preclinical investigations. Background of the study.:TMPRSS2-ERG junction oncogene is present in more than 50% of patients with prostate cancer, and its expression is frequently associated with poor prognosis. We knockdown by siRNA the two TMPRSS2-ERG fusion variants (III and IV) most frequently identified in patients’ biopsies and found an inhibition of TMPRSS2-ERG of above 70% in human prostate cancer VCaP cell line expressing TMPRSS2-ERG junction oncogene. To point out genes regulated after TMPRSS2-ERG oncogene silencing, microarray analysis was performed.. Materiel and Methods. Human prostate cancer VCaP cell line expressing TMPRSS2-ERG oncogene (ATCC® CRL-2876™ Manassas, USA) was grown in Dulbecco's Modified Eagle Medium (DMEM) (Invitrogen, Cergy-Pontoise, France) supplemented with 10% fetal bovine serum (FBS), 100 units/ml penicillin and 100 μg/ml streptomycin (Invitrogen). Cells were incubated at 37°C in a humidified atmosphere containing 5% CO2. Transfection was carried out using Lipofectamine RNAiMAX transfecting agent (Invitrogen) according to manufacturer's instructions. Briefly, 8×105 VCaP cells were seeded in six-well plates in DMEM supplemented with 10% FCS, penicillin (100U/ml) and streptomycin (10µg/ml) and transfected with 50 nM siRNA TMPRSS2-ERG III, siRNA TMPRSS2-ERG IV and siRNA Control and 6 μL Lipofectamine® RNAiMAX. Cells were incubated with siRNA for 48h. At the end of the treatments, total RNAs of untreated cells (NT) and transfected cells were extracted using RNeasy mini-kit (Quiagen, Courtaboeuf, France). Three independent experiments were performed. Results. Microarray analysis confirmed ERG inhibition by both siRNA TMPRSS2-ERG III and IV and revealed a common down-regulated gene, ADRA2A, involved in cell proliferation and migration. Experiments are performed with Agilent Whole Genome 8x60K (028004) microarray. In triplicate with a non treated control cells, a control with ascramble siRNA, a siRNA TMPRSS2-ERG III, a siRNA TMPRSS2 IV.
2015-01-09 | E-MTAB-2838 | biostudies-arrayexpress
Project description:Here, we developed immunoprecipitation-mass spectrometry assays for the measurement of a low-abundance T1E4 TMPRSS2-ERG fusion protein, its isoforms and its interactome in VCaP prostate cancer cells.
2021-03-29 | PXD021236 | Pride
Project description:<p>Half of prostate cancers harbor gene fusions between <i>TMPRSS2</i> and members of the <i>ETS</i> transcription factor family. To date little is known about the presence of non-ETS fusion events in prostate cancer. We employed next-generation transcriptome sequencing (RNA-Seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes <i>ETV1</i> and <i>ERG</i>, and five involving non-ETS genes such as <i>CDKN1A</i> (p21), <i>CD9</i> and <i>IKBKB</i> (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene <i>RSRC2</i>. The novel gene fusions are found to be of low frequency but interestingly, the non-ETS fusions were all present in prostate cancer harboring the <i>TMPRSS2-ERG</i> gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement prone phenotype.</p>
| phs000310 | dbGaP
Project description:Prostate tumors with the gene fusion TMPRSS2:ERG have been reported to have a significantly higher risk of recurrence compared with tumors lacking the fusion. Tumors from 139 patients who underwent radical prostatectomy were analyzed for the expression of 502 cancer-related genes to identify genes differentially regulated in TMPRSS2:ERG fusion tumors as well as identify biomarkers of biochemical recurrence.
2009-10-23 | GSE18655 | GEO