Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA177576 | ENA |
REPOSITORIES: ENA
Similar Datasets
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
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:<p>BRCA1 mutations are a hallmark of hereditary ovarian cancer, strongly linked to deficiencies in homologous recombination (HR) DNA repair and impaired DNA replication fork protection. However, its roles in cancer progression beyond maintaining genomic integrity remain poorly understood. Through metabolomics approaches, we found BRCA1-deficiency strikingly increased choline metabolism. Loss of BRCA1 promotes choline uptake through upregulating choline transporter-like protein 4 (CTL4). BRCA1 directly binds and recruits EZH2-mediated H3K27Me3 deposition to CTL4 promoter. CTL4 was therefore overexpressed in ovarian cancer tissues with BRCA1 mutations. Furthermore, BRCA1-deficiency significantly promotes ovarian cancer invasion, while inhibition of CTL4 reverses the high metastatic potential of BRCA1-deficient ovarian cancer cells, suggesting the functionality and specificity of CTL4 as a therapeutic target. Additionally, we discovered that phosphocholine, the choline metabolite increased by CTL4 overexpression, interacted with and stabilized the epithelial-to-mesenchymal transition inducer FAM3C in BRCA1-deficient ovarian cancer cells. Importantly, we identified a potent CTL4 inhibitor, DT-13, which significantly reduces choline metabolism and effectively suppresses metastasis in BRCA1-deficient ovarian cancers. Therefore, our study uncovers a mechanism underlying metastasis in BRCA1-deficient cancers and identifies CTL4 as a therapeutic target for metastatic ovarian cancer patients with BRCA1 mutations.</p>
2026-05-15 | MTBLS12245 | MetaboLights
Project description:Bladder cancer is one of the most common genitourinary malignancies worldwide. It is a heterogeneous disease at the clinical, pathological, and genetic levels. In an exome-sequencing study of bladder cancer, we identified genes mutated in bladder cancer coding for proteins involved in chromatin modification, cell division, and DNA repair. STAG2, a constituent of the cohesin complex, was commonly mutated or lost, mainly in tumors of low stage or grade. Loss of STAG2 expression was often observed in genomically stable tumors, suggesting that STAG2 may act as a tumor suppressor through mechanisms other than chromosome segregation (Balbás-Martínez et al. 2013). In addition to mediating sister chromatid cohesion, cohesin plays a central role in DNA looping and organization of the genome into Topologically Associating Domains (TADs). Two variant cohesin complexes that contain either STAG1 or STAG2 are present in all cell type. Here we addressed their genome wide binding in bladder cancer cells.
2021-03-15 | GSE111913 | GEO
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
Project description:Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy [GPL6984]
| PRJNA224157 | ENA
Project description:Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy [GPL6983]
| PRJNA224155 | ENA
Project description:Truncating mutations of the tumor suppressor gene STAG2, encoding a component of the chromatin-bound cohesin complex, are present in many human cancer types. Here we report for the first time the early effects of reconstituting physiological levels of wild-type STAG2 in STAG2-mutant human cancer cells. Acute STAG2 reconstitution only modestly affected global gene expression - <1% of genes were altered by two-fold or greater. Only EFEMP1, encoding a secreted extracellular matrix glycoprotein, was induced by STAG2 in all experimental systems tested. There were similarly modest effects on chromatin loops - <1% of all chromatin loops were altered in intensity. and no loops were entirely STAG2-dependent. Loops strengthened by STAG2 reconstitution tended to be small, consistent with prior observations that STAG2-cohesin has less loop extrusion processivity than STAG1-cohesin. The STAG2-regulated “immediate early genes” were not accompanied by STAG2-regulated enhancer-promoter chromatin loops and no chromatin features were identified by integrative bioinformatics with newly generated ChIP-seq and ATAC-seq data that could explain their regulation by STAG2. Together these data indicate that the number of genes directly regulated by STAG2-cohesin is small, suggest that current models are likely insufficient to explain the mechanism of direct transcriptional regulation by STAG2-cohesin, and identify EFEMP1 as a potential effector of STAG2 tumor suppression.
2026-02-09 | GSE318552 | GEO
Project description:Truncating mutations of the tumor suppressor gene STAG2, encoding a component of the chromatin-bound cohesin complex, are present in many human cancer types. Here we report for the first time the early effects of reconstituting physiological levels of wild-type STAG2 in STAG2-mutant human cancer cells. Acute STAG2 reconstitution only modestly affected global gene expression - <1% of genes were altered by two-fold or greater. Only EFEMP1, encoding a secreted extracellular matrix glycoprotein, was induced by STAG2 in all experimental systems tested. There were similarly modest effects on chromatin loops - <1% of all chromatin loops were altered in intensity. and no loops were entirely STAG2-dependent. Loops strengthened by STAG2 reconstitution tended to be small, consistent with prior observations that STAG2-cohesin has less loop extrusion processivity than STAG1-cohesin. The STAG2-regulated “immediate early genes” were not accompanied by STAG2-regulated enhancer-promoter chromatin loops and no chromatin features were identified by integrative bioinformatics with newly generated ChIP-seq and ATAC-seq data that could explain their regulation by STAG2. Together these data indicate that the number of genes directly regulated by STAG2-cohesin is small, suggest that current models are likely insufficient to explain the mechanism of direct transcriptional regulation by STAG2-cohesin, and identify EFEMP1 as a potential effector of STAG2 tumor suppression.
2026-02-09 | GSE318550 | GEO
Project description:Frequent mutations in human breast cancer tumors detected with Ion Torrent Ampliseq Cancer Panel
| PRJNA233537 | ENA