Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA224155 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy [GPL6984]
| PRJNA224157 | ENA
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: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: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
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-51640 | biostudies-arrayexpress
Project description:Frequent truncating mutations of STAG2 in bladder cancer
| PRJNA177576 | ENA
Project description:The maintenance of quiescence is essential for tissue homeostasis. STAG2 is one of the few genes mutated in the normal urothelium of organ donors, with mutant cells undergoing positive selection 1. STAG2 is also a major tumour suppressor gene 2–4 and its inactivation is an early event in bladder carcinogenesis 1,3. However, the mechanisms through which STAG2, a cohesin component, disrupt urothelial homeostasis remain largely unknown. Here, we show that, in normal murine urothelial cells, Stag2 inactivation disrupts differentiation programs, induces a transient cell cycle entry, and primes cells for clonal expansion under stress conditions. In addition, STAG2 loss in urothelial cells expressing mutant FGFR3 —the most important bladder cancer oncogene 5— enhances tumour formation. For the first time, we show that STAG2 co-operates with the transcriptional complex DREAM, a master regulator of quiescence 6,7, binding to common genomic sites, including genes involved in cell cycle control. STAG2 loss results in changes in the expression of DREAM targets, its composition and chromatin distribution, and in the rewiring of chromatin interactions involving DREAM binding motifs in genes critical for cell cycle entry. Our findings provide strong evidence that STAG2 loss leads to changes in 3D genome organization through a novel mechanism involving the DREAM complex, leading to the disruption of homeostatic quiescence and oncogenic sensitivity.
2026-02-03 | GSE288725 | GEO
Project description:The maintenance of quiescence is essential for tissue homeostasis. STAG2 is one of the few genes mutated in the normal urothelium of organ donors, with mutant cells undergoing positive selection 1. STAG2 is also a major tumour suppressor gene 2–4 and its inactivation is an early event in bladder carcinogenesis 1,3. However, the mechanisms through which STAG2, a cohesin component, disrupt urothelial homeostasis remain largely unknown. Here, we show that, in normal murine urothelial cells, Stag2 inactivation disrupts differentiation programs, induces a transient cell cycle entry, and primes cells for clonal expansion under stress conditions. In addition, STAG2 loss in urothelial cells expressing mutant FGFR3 —the most important bladder cancer oncogene 5— enhances tumour formation. For the first time, we show that STAG2 co-operates with the transcriptional complex DREAM, a master regulator of quiescence 6,7, binding to common genomic sites, including genes involved in cell cycle control. STAG2 loss results in changes in the expression of DREAM targets, its composition and chromatin distribution, and in the rewiring of chromatin interactions involving DREAM binding motifs in genes critical for cell cycle entry. Our findings provide strong evidence that STAG2 loss leads to changes in 3D genome organization through a novel mechanism involving the DREAM complex, leading to the disruption of homeostatic quiescence and oncogenic sensitivity.
2026-02-03 | GSE288819 | GEO
Project description:The maintenance of quiescence is essential for tissue homeostasis. STAG2 is one of the few genes mutated in the normal urothelium of organ donors, with mutant cells undergoing positive selection 1. STAG2 is also a major tumour suppressor gene 2–4 and its inactivation is an early event in bladder carcinogenesis 1,3. However, the mechanisms through which STAG2, a cohesin component, disrupt urothelial homeostasis remain largely unknown. Here, we show that, in normal murine urothelial cells, Stag2 inactivation disrupts differentiation programs, induces a transient cell cycle entry, and primes cells for clonal expansion under stress conditions. In addition, STAG2 loss in urothelial cells expressing mutant FGFR3 —the most important bladder cancer oncogene 5— enhances tumour formation. For the first time, we show that STAG2 co-operates with the transcriptional complex DREAM, a master regulator of quiescence 6,7, binding to common genomic sites, including genes involved in cell cycle control. STAG2 loss results in changes in the expression of DREAM targets, its composition and chromatin distribution, and in the rewiring of chromatin interactions involving DREAM binding motifs in genes critical for cell cycle entry. Our findings provide strong evidence that STAG2 loss leads to changes in 3D genome organization through a novel mechanism involving the DREAM complex, leading to the disruption of homeostatic quiescence and oncogenic sensitivity.
2026-02-03 | GSE288712 | GEO