Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

STAG2 loss-of-function affects short-range genomic contacts and modulates urothelial differentiation in bladder cancer cells

ABSTRACT: STAG2 loss-of-function affects short-range genomic contacts and modulates urothelial differentiation in bladder cancer cells

PROVIDER: PRJNA649548 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12344686_1.fastq.gz	Fastqsanger.gz
	SRR12344686_2.fastq.gz	Fastqsanger.gz
	SRR12344687_1.fastq.gz	Fastqsanger.gz
	SRR12344687_2.fastq.gz	Fastqsanger.gz
	SRR12344688_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 6

Similar Datasets

STAG2 loss-of-function affects short-range genomic contacts and modulates urothelial differentiation in bladder cancer cells

Project description:Cohesin exists in two variants, containing either STAG1 or STAG2. STAG2 is one of the most commonly mutated genes in human cancer, and a major bladder cancer tumor suppressor. Little is known about how its inactivation contributes to tumor development. Here, we analyze the genomic distribution of STAG1 and STAG2 and perform STAG2 loss-of-function experiments using RT112 bladder cancer cells; we then analyze the resulting genomic effects by integrating gene expression and chromatin interaction data.

2020-07-30 | GSE155380 | GEO

Truncating mutations of STAG2 define a molecular subgroup of aneuploid bladder cancers with poor prognosis.

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

Frequent truncating mutations of STAG2 in bladder cancer

Project description:Here we report the discovery of truncating mutations of the gene encoding the cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation, in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive urothelial carcinomas of the bladder. Our studies suggest that STAG2 has a role in controlling chromosome number but not the proliferation of bladder cancer cells. These findings identify STAG2 as one of the most commonly mutated genes in bladder cancer. Affymetrix CytoScan HD Arrays were performed according to the manufacturer's directions on genomic DNA extracted directly from 12 snap-frozen human urothelial carcinoma primary tumors with somatic mutations of the STAG2 gene.

2013-06-30 | GSE41581 | GEO

STAG2 loss-of-function affects short-range genomic contacts and modulates the basal-luminal transcriptional program of bladder cancer cells.

Project description:Cohesin exists in two variants containing STAG1 or STAG2. STAG2 is one of the most mutated genes in cancer and a major bladder tumor suppressor. Little is known about how its inactivation contributes to tumorigenesis. Here, we analyze the genomic distribution of STAG1 and STAG2 and perform STAG2 loss-of-function experiments using RT112 bladder cancer cells; we then analyze the genomic effects by integrating gene expression and chromatin interaction data. Functional compartmentalization exists between the cohesin complexes: cohesin-STAG2 displays a distinctive genomic distribution and mediates short and mid-ranged interactions that engage genes at higher frequency than those established by cohesin-STAG1. STAG2 knockdown results in down-regulation of the luminal urothelial signature and up-regulation of the basal transcriptional program, mirroring differences between STAG2-high and STAG2-low human bladder tumors. This is accompanied by rewiring of DNA contacts within topological domains, while compartments and domain boundaries remain refractive. Contacts lost upon depletion of STAG2 are assortative, preferentially occur within silent chromatin domains, and are associated with de-repression of lineage-specifying genes. Our findings indicate that STAG2 participates in the DNA looping that keeps the basal transcriptional program silent and thus sustains the luminal program. This mechanism may contribute to the tumor suppressor function of STAG2 in the urothelium.

| S-EPMC8565347 | biostudies-literature

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1

Project description:Cohesin complexes carrying STAG1 or STAG2 organize the genome into chromatin loops. STAG2 loss-of-function mutations promote metastasis in Ewing sarcoma, a pediatric cancer that is driven by the fusion transcription factor EWS-FLI1. We have integrated transcriptomic data from patients and cellular models to identify a STAG2-dependent gene signature associated with worse prognosis. Subsequent genomic profiling and high-resolution chromatin interaction data from Capture Hi-C indicate that cohesin-STAG2 facilitates the communication between EWS-FLI1-bound long GGAA repeats acting as neoenhancers and their target promoters. Changes in CTCF-dependent chromatin contacts, unrelated to EWS-FLI1 binding, also contribute to the aggressive phenotype. STAG1 is unable to compensate for STAG2 loss and chromatin-bound cohesin is severely decreased, while levels of the processivity factor NIPBL remain unchanged, resulting in altered DNA looping dynamics. These results illuminate how STAG2 loss rewires the Ewing sarcoma chromatin interactome to promote metastasis and provide a list of potential biomarkers and therapeutic targets.

2024-09-18 | GSE267222 | GEO

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1

2024-09-18 | GSE267220 | GEO

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1

2024-09-18 | GSE267221 | GEO

Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy [GPL6984]

Project description:STAG2 is a novel UBC tumor suppressor acting through mechanisms that are different from its role to prevent aneuploidy Gene copy number analyses of STAG2 in urinary bladder tumors. R values were extracted from beadstudio and normalised using the pounds method. Log R Ratios were calculated using an average value of R from 200 cases and controls from the Epicuro study. WaviCGH was used to generate copy number calls and log R ratios in the region of STAG2 on the X chromosome were also visualised manually to determine STAG2 loss.

2013-10-24 | E-GEOD-51589 | biostudies-arrayexpress

Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy [GPL6983]

2013-10-24 | E-GEOD-51640 | biostudies-arrayexpress

Transcriptome analysis for KDM6A mutated urothelial bladder carcinoma and EZH2 inhibitor treated KDM6A mutated urothelial bladder carcinoma

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data