Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA368806 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Rhabdoid Tumors (RT) are highly aggressive tumors that are frequently localized in the central nervous system (CNS) where they are termed atypical teratoid and rhabdoid tumors (ATRT). We generated conditional Smarcb1-deficient mouse model leads to CNS Smarcb1-deficient tumors. We used microarrays to compared gene expression profilings of various human and mouse tumors. Our data demonstrate that the Smarcb1-deficient mouse model recapitulates the diversity of human RT.
2016-01-27 | GSE64019 | GEO
Project description:SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice. Profiling Smarcb1 dependent gene expression we find genes which are dependent on Smarcb1 expression to be enriched for ECM and cell adhesion functions. We identify Igfbp7, which is related to the insulin-like growth factor binding proteins family, as a downstream target of Smarcb1 transcriptional activity, and show that re-introduction of Igfbp7 alone can hinder tumor development. Two cancer cell lines, 167 and 365, derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice were re-infected with a retro-viral vector for Smarcb1 re-expression or an empty retro-viral vector as control. Total-RNA was collected 3 days post infection so as to enrich for direct targets of Smarcb1 transcriptionaly regulated genes
2013-12-31 | E-GEOD-46017 | biostudies-arrayexpress
Project description:Germline mutations of the SMARCB1 gene predispose to two distinct tumor syndromes: rhabdoid tumor predisposition syndrome, with malignant pediatric tumors mostly developing in brain and kidney, and familial schwannomatosis, with adulthood benign tumors involving cranial and peripheral nerves. The mechanisms by which SMARCB1 germline mutations predispose to rhabdoid tumors versus schwannomas are still unknown. Here, to understand the origin of these two types of SMARCB1-associated tumors, we generated different tissue- and developmental stage-specific conditional knockout mice carrying Smarcb1 and/or Nf2 deletion. Smarcb1 loss in early neural crest was necessary to initiate tumorigenesis in the cranial nerves and meninges with typical histological features and molecular profiles of human rhabdoid tumors. By inducing Smarcb1 loss at later developmental stage in the Schwann cell lineage, in addition to biallelic Nf2 gene inactivation, we generated the first mouse model developing schwannomas with the same underlying gene mutations found in schwannomatosis patients.
2017-10-31 | GSE94082 | GEO
Project description:SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice. Profiling Smarcb1 dependent gene expression we find genes which are dependent on Smarcb1 expression to be enriched for ECM and cell adhesion functions. We identify Igfbp7, which is related to the insulin-like growth factor binding proteins family, as a downstream target of Smarcb1 transcriptional activity, and show that re-introduction of Igfbp7 alone can hinder tumor development.
2013-12-31 | GSE46017 | GEO
Project description:Renal medullary carcinomas (RMC) are rare aggressive tumors of the kidneys, characterized by a -mostly- biallelic loss of SMARCB1. Characteristically, these tumors arise in patients with sickle cell trait or other hemoglobinopathies. Recent molecular and landscaping characterization efforts have unraveled oncogenic pathways that drive tumorigenesis. Among these, gene sets that characterize replicative stress and the innate immune response are upregulated in RMCs. Despite comprehensive genetic and transcriptomic characterizations, commonalities or differences to other SMARCB1 deficient entities so far have not been investigated. We analyzed the methylome of four novel primary RMC and compared it to other, SMARCB1 deficient entities such as rhabdoid tumors (RT) and epithelioid sarcomas using 850K methylation arrays. In accordance with previous gene expression data, we find that RMCs separate from other SMARCB1 deficient entities such as extra-and intracranial rhabdoid tumors, pointing to a potentially different cell of origin and a role of additional mutations or genetic aberrations that may drive tumorigenesis and thus alter the methylome when compared to rhabdoid tumors. In a focused analysis of genes that are important for nephrogenesis, we detected particularly genes that govern early nephrogenesis such as FOXI to be hypomethylated and expressed at high levels in RMC. Overall, our analyses underscore the fact that RMCs represent a separate entity with limited similarities to rhabdoid tumors warranting specific treatment, tailored to the aggressiveness of the disease.
2022-11-02 | GSE211942 | GEO
Project description:We used microarrays to compared gene re-expression of SMARCB1 in I2A SMARCB1-deficient rhabdoid tumor cell line.
2017-11-02 | GSE98277 | GEO
Project description:Transcriptional response to Smarcb1 re-expression in murine derived Smarcb1 deficient p53 null tumors
| PRJNA196906 | ENA
Project description:To characterize tumors developing in our SMARCB1 deficient mouse model, we performed mRNA sequencing of tumors and control normal tissues
2019-09-19 | GSE137633 | GEO
Project description:The multi-subunit ATP-dependent chromatin remodeling complex BAF ('mammalian SWI/SNF complex') regulates DNA accessibility during cell fate transitions and functions as a context-dependent tumor suppressor. SMARCB1, as a one of the component of BAF complex, was first found to be biallelically inactivated in ~98% of all malignant rhabdoid tumors (MRT), aggressive pediatric tumors that can occur cranially or extracranially. To examine the mechanisms through which inactivation of SMARCB1 drives malignant rhabdoid tumorigenesis, we conducted RNAseq studies in BT-12 cells reconstituted with either WT or M4 mutant (an in-frame deletion (185-193D) was identified from tumor patient) SMARCB1. These results indicate that loss of SMARCB1 promotes cell proliferation but also impairs cell adhesion and migration, consistent with the hypothesis that SMARCB1 exerts its tumor suppressive function predominantly by inhibiting proliferation. We applied the RNA-Seq to provide the transcriptomic profiling of BT-12 cell lines without or with stable expression of SMARCB1.
2020-10-01 | GSE139262 | GEO
Project description:Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets. 49 ATRT samples were selected for RNA extraction and hybridization on Affymetrix Affymetrix Human Genome U133 Plus 2.0 Arrays. ---------------------------------------- This submission consists of the expression data for 49 of 170 samples only
2016-03-02 | E-GEOD-70678 | biostudies-arrayexpress