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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE51641 | GEO | 2013/10/24

SECONDARY ACCESSION(S): PRJNA224153

REPOSITORIES: GEO

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

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-10-24 | E-GEOD-51641 | biostudies-arrayexpress

Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy.

Project description:Urothelial bladder cancer (UBC) is heterogeneous at the clinical, pathological and genetic levels. Tumor invasiveness (T) and grade (G) are the main factors associated with outcome and determine patient management. A discovery exome sequencing screen (n = 17), followed by a prevalence screen (n = 60), identified new genes mutated in this tumor coding for proteins involved in chromatin modification (MLL2, ASXL2 and BPTF), cell division (STAG2, SMC1A and SMC1B) and DNA repair (ATM, ERCC2 and FANCA). STAG2, a subunit of cohesin, was significantly and commonly mutated or lost in UBC, mainly in tumors of low stage or grade, and its loss was associated with improved outcome. Loss of expression was often observed in chromosomally stable tumors, and STAG2 knockdown in bladder cancer cells did not increase aneuploidy. STAG2 reintroduction in non-expressing cells led to reduced colony formation. Our findings indicate that STAG2 is a new UBC tumor suppressor acting through mechanisms that are different from its role in preventing aneuploidy.

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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.

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

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

Project description:STAG2 is a novel UBC tumor suppressor acting through mechanisms that are different from its role to prevent aneuploidy

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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

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Mutational inactivation of STAG2 causes aneuploidy in human cancer.

Project description:Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins of aneuploidy through integrative genomic analyses of human tumors. A diverse range of tumor types were found to harbor deletions or inactivating mutations of STAG2, a gene encoding a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Because STAG2 is on the X chromosome, its inactivation requires only a single mutational event. Studying a near-diploid human cell line with a stable karyotype, we found that targeted inactivation of STAG2 led to chromatid cohesion defects and aneuploidy, whereas in two aneuploid human glioblastoma cell lines, targeted correction of the endogenous mutant alleles of STAG2 led to enhanced chromosomal stability. Thus, genetic disruption of cohesin is a cause of aneuploidy in human cancer.

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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