Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA358425 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5124440_1.fastq.gz | Fastqsanger.gz | |||
| SRR5124440_2.fastq.gz | Fastqsanger.gz | |||
| SRR5124450_1.fastq.gz | Fastqsanger.gz | |||
| SRR5124450_2.fastq.gz | Fastqsanger.gz | |||
| SRR5124460_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 100 |
Similar Datasets
Project description:Purpose: The goals of this study are to compare 1. The transcription profile in KDM6A wildtype and KDM6A mutated urothelial bladder carcinoma. 2. The transcriptional changes in KDM6A mutated urothelial bladder carcinoma upon EZH2 inhibitor treatment.
2017-03-01 | GSE92723 | GEO
Project description:Metastatic urothelial carcinoma of the bladder is generally incurable with current systemic therapies. Chromatin modifiers are frequently mutated in bladder cancer, with ARID1A inactivating mutations present in 20% of tumors. EZH2 is a histone methyltransferase that acts as an oncogene that functionally opposes ARID1A. In addition, PI3K signaling is activated in over 20% of bladder cancers. Here we show that ARID1A-mutant tumors are more sensitive to EZH2 inhibition than ARID1A-wild-type tumors. Mechanistic studies reveal that: 1) ARID1A deficiency results in a dependency on PI3K/AKT/mTOR signaling via upregulation of a non-canonical PI3K regulatory subunit PIK3R3, and: 2) EZH2 inhibitor sensitivity is due to upregulation of PIK3IP1, an inhibitor protein of PI3K signaling. Thus, our studies suggest that a subset of bladder cancers with ARID1A mutations can be treated with inhibitors of EZH2 and/or PI3K, and reveal novel mechanistic insights into the role of non-canonical PI3K constituents in bladder cancer biology.
2022-08-22 | GSE183777 | GEO
Project description:The UTX/KDM6A gene encodes the UTX histone H3K27 demethylase, which plays an important role in mammalian development and is frequently mutated in cancers and particularly, in urothelial cancers. Using BioID technique, we explored the interactome of different UTX isoforms.
2024-01-28 | PXD041254 | Pride
Project description:Aneuploidy is among the most common hallmarks of cancer, yet the underlying genetic mechanisms are still poorly defined. We have recently identified STAG2 as a gene that is mutated in human cancer and whose inactivation leads directly to chromosomal instability and aneuploidy. However, no single tumor type has yet been identified in which inactivation of a cohesin subunit represents a predominant mutational event. Here we used immunohistochemistry to screen a panel of 2,214 tumors from each of the major human tumor types to identify additional tumor types harboring somatic loss of STAG2. Strikingly, STAG2 expression was completely absent in 18% of urothelial carcinomas, the most common type of bladder cancer and the fifth most common cancer in the United States. DNA sequencing revealed that somatic mutations of STAG2 were present in 21% of urothelial carcinomas, which were found to be a group of highly aneuploid tumors. The acquisition of STAG2 mutations was shown to be an early event in the pathogenesis of urothelial carcinoma. STAG2 loss was significantly associated with lymph node invasion, increased disease recurrence, and reduced cancer-specific survival. These results identify STAG2 as one of the most commonly mutated genes in bladder cancer discovered to date, and demonstrate that STAG2 inactivation defines an aggressive subtype of bladder cancer with particularly poor prognosis. Affymetrix CytoScan HD Arrays were performed according to the manufacturer's directions on genomic DNA extracted directly from snap-frozen human urothelial carcinoma primary tumors. Copy number analysis using Affymetrix CytoScan HD Arrays was performed for 12 human urothelial carcinomas of the bladder with truncating mutations of the STAG2 gene.
2013-06-30 | E-GEOD-41581 | biostudies-arrayexpress
Project description:ARID1A, an epigentic modifier, is often mutated in ovarian clear cell carcinoma (OCCC). In addition, EZH2 is frequently upregulated in OCCC. Inhibtion of EZH2 with an inhibitor (GSK126) selectively inhibits ARID1A-mutated cells. This study was designed to understand changes in gene expression profiles following EZH2 inhibition or ARID1A restoration. Chromatin remodelers such as ARID1A are frequently mutated in a broad array of cancers. However, targeted cancer therapy based on ARID1A mutation status has not been described. Intriguingly, ARID1A mutated cancers typically lack genomic instability, suggesting significant involvement of epigenetic mechanisms. Here we show that inhibition of the EZH2 methyltransferase acts in a synthetic lethal manner in ARID1A mutated cells. Remarkably, ARID1A mutation status correlated with response to EZH2 inhibitor. Genome-wide profiling revealed antagonistic roles of ARID1A and EZH2 in gene regulation. Further, we identified PIK3IP1 as a direct ARID1A/EZH2 target gene whose upregulation contributes to the observed synthetic lethality in the EZH2 inhibitor treated ARID1A mutated cells. Significantly, EZH2 inhibitor caused the regression of established ARID1A mutated tumors in vivo. Together, this data demonstrate a synthetic lethality between ARID1A mutation and EZH2 inhibition. They indicate that pharmacological inhibition of EZH2 represents a novel treatment strategy for ARID1A mutated cancers.
2015-01-20 | E-GEOD-54979 | biostudies-arrayexpress
Project description:Advanced bladder cancer remains a difficult cancer to treat, and for the majority of patients, current standard treatments ultimately prove ineffective. These tumors frequently harbor mutations in the BAF complex subunit ARID1A, which has been reported to confer sensitivity to EZH2 inhibition in several tumor types. Here we describe the generation of CPI-0209, a best-in-class, orally available EZH2 inhibitor. We show that mutant bladder cancer lines harboring ARID1A loss of function (LOF) mutations are preferentially sensitive to inhibition of EZH2. Treatment with CPI-0209 not only elicits a significant monotherapeutic response in ARID1A mutant models, it also outperforms cisplatin and improves response in chemo-resistant models. These findings shine light on new therapeutic opportunities for patients with advanced urothelial carcinoma.
2024-06-26 | GSE176490 | GEO
Project description:Advanced bladder cancer remains a difficult cancer to treat, and for the majority of patients, current standard treatments ultimately prove ineffective. These tumors frequently harbor mutations in the BAF complex subunit ARID1A, which has been reported to confer sensitivity to EZH2 inhibition in several tumor types. Here we describe the generation of CPI-0209, a best-in-class, orally available EZH2 inhibitor. We show that mutant bladder cancer lines harboring ARID1A loss of function (LOF) mutations are preferentially sensitive to inhibition of EZH2. Treatment with CPI-0209 not only elicits a significant monotherapeutic response in ARID1A mutant models, it also outperforms cisplatin and improves response in chemo-resistant models. These findings shine light on new therapeutic opportunities for patients with advanced urothelial carcinoma.
2024-06-26 | GSE176486 | GEO
Project description:Advanced bladder cancer remains a difficult cancer to treat, and for the majority of patients, current standard treatments ultimately prove ineffective. These tumors frequently harbor mutations in the BAF complex subunit ARID1A, which has been reported to confer sensitivity to EZH2 inhibition in several tumor types. Here we describe the generation of CPI-0209, a best-in-class, orally available EZH2 inhibitor. We show that mutant bladder cancer lines harboring ARID1A loss of function (LOF) mutations are preferentially sensitive to inhibition of EZH2. Treatment with CPI-0209 not only elicits a significant monotherapeutic response in ARID1A mutant models, it also outperforms cisplatin and improves response in chemo-resistant models. These findings shine light on new therapeutic opportunities for patients with advanced urothelial carcinoma.
2024-06-26 | GSE176477 | GEO
Project description:Advanced bladder cancer remains a difficult cancer to treat, and for the majority of patients, current standard treatments ultimately prove ineffective. These tumors frequently harbor mutations in the BAF complex subunit ARID1A, which has been reported to confer sensitivity to EZH2 inhibition in several tumor types. Here we describe the generation of CPI-0209, a best-in-class, orally available EZH2 inhibitor. We show that mutant bladder cancer lines harboring ARID1A loss of function (LOF) mutations are preferentially sensitive to inhibition of EZH2. Treatment with CPI-0209 not only elicits a significant monotherapeutic response in ARID1A mutant models, it also outperforms cisplatin and improves response in chemo-resistant models. These findings shine light on new therapeutic opportunities for patients with advanced urothelial carcinoma.
2024-06-26 | GSE176485 | GEO
Project description:Advanced bladder cancer remains a difficult cancer to treat, and for the majority of patients, current standard treatments ultimately prove ineffective. These tumors frequently harbor mutations in the BAF complex subunit ARID1A, which has been reported to confer sensitivity to EZH2 inhibition in several tumor types. Here we describe the generation of CPI-0209, a best-in-class, orally available EZH2 inhibitor. We show that mutant bladder cancer lines harboring ARID1A loss of function (LOF) mutations are preferentially sensitive to inhibition of EZH2. Treatment with CPI-0209 not only elicits a significant monotherapeutic response in ARID1A mutant models, it also outperforms cisplatin and improves response in chemo-resistant models. These findings shine light on new therapeutic opportunities for patients with advanced urothelial carcinoma.
2024-06-26 | GSE176362 | GEO