High-throughput gene expression profilng of SMARCA4-mutated extra-cranial rhabdoid tumours (ECRT-SMARCA4), SMARCB1-mutated ECRT, ATRT and SCCOHT tumours by RNA sequencing
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PROVIDER: PRJNA734266 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: Molecular characterization of ECRT-SMARCA4 tumours and their place within the constellation of ECRT-SMARCB1, ATRT and SCCOHT Methods: Total RNA was obtained from 72 fresh-frozen tumour samples using the Qiagen RNAeasy kit (Qiagen, Venlo, Netherlands), according to the manufacturer’s procedure. Barcode Illumina compatible libraries were generated from 750 ng of total RNA for each sample using the TruSeq Stranded mRNA Library Preparation Kit (Illumina). Libraries were sequenced using the Illumina HiSeq 2500 platform. RNA-seq data pre-processing was performed using an in-house pipeline developed at the Curie Institute Bioinformatics Core Facility. Read mapping and counting were performed using STAR, version 2.5.3) and the hg19 version of the human reference genome. Results: Dimensionality reduction and hierarchical clustering algorithms applied to the transcriptomics dataset show that ECRT-SMARCA4 display molecular features intermediate between SCCOHT and ECRTS-MARCB1.
2021-06-02 | GSE175891 | GEO
Project description:Extracranial rhabdoid tumours (ECRT) are an aggressive malignancy of infancy and early childhood. The vast majority of cases demonstrate inactivation of SMARCB1 (ECRT_SMARCB1) but, rarely, ECRT can harbour the alternative inactivation of SMARCA4 (ECRT_SMARCA4) instead of SMARCB1. To explore the place of ECRTSMARCA4 in the "rhabdoid tumour" spectrum, we generated and collected from previous studies genome-wide DNA methylation array data (n = 85) from Atypical/Teratoid Rhabdoid Tumours (ATRT), ECRT_SMARCB1, ECRT_SMARCA4 and small cell carcinomas of the ovary, hypercalcaemic type (SCCOHT) tumours. Using dimensionality reduction and unsupervised clustering approaches, our results demonstrate that ECRT_SMARCA4 display an intermediate DNA methylation profile between SCCOHT and ECRT_SMARCB1.
2021-06-02 | GSE175892 | 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
Project description:Atypical teratoid/rhabdoid tumors (ATRT) are known for their heterogeneity concerning pathophysiology and outcome. However, predictive factors within distinct subgroups still need to be uncovered. Using multiplex immunofluorescent staining and singe-cell RNA sequencing we unraveled distinct compositions of the immunological tumor microenvironment (TME) across ATRT subgroups. CD68+ cells predominantly infiltrate ATRT-SHH and ATRT-MYC and are a negative prognostic factor for patients’ survival. Within the murine ATRT-MYC and ATRT-SHH TME, Cd68+ macrophages are core to intercellular communication with tumor cells. In ATRT-MYC distinct tumor cell phenotypes express macrophage marker genes. These cells are involved in the acquisition of chemotherapy resistance in our relapse xenograft mouse model. In conclusion, the tumor cell-macrophage interaction contributes to ATRT-MYC heterogeneity and tumor recurrence.
2020-05-14 | GSE141533 | GEO
Project description:Atypical teratoid/rhabdoid tumors (ATRT) are known for their heterogeneity concerning pathophysiology and outcome. However, predictive factors within distinct subgroups still need to be uncovered. Using multiplex immunofluorescent staining and singe-cell RNA sequencing we unraveled distinct compositions of the immunological tumor microenvironment (TME) across ATRT subgroups. CD68+ cells predominantly infiltrate ATRT-SHH and ATRT-MYC and are a negative prognostic factor for patients’ survival. Within the murine ATRT-MYC and ATRT-SHH TME, Cd68+ macrophages are core to intercellular communication with tumor cells. In ATRT-MYC distinct tumor cell phenotypes express macrophage marker genes. These cells are involved in the acquisition of chemotherapy resistance in our relapse xenograft mouse model. In conclusion, the tumor cell-macrophage interaction contributes to ATRT-MYC heterogeneity and tumor recurrence.
2020-05-14 | GSE141532 | GEO
Project description:Almost all medulloblastomas (MB) of the Wingless/Int-1 (WNT) subgroup are characterized by hotspot mutations in CTNNB1, and mouse models have convincingly demonstrated the tumor-initiating role of these mutations. Additional alterations in SMARCA4 are detected in around 20 % of WNT MB but their functional role is mostly unknown. We therefore amended previously described Blbp-cre::Ctnnb1(ex3)fl/wt mice by the introduction of a floxed Smarca4 allele. In contrast to existing literature, even mutated β-catenin on its own in our Blbp-cre::Ctnnb1(ex3)fl/wt mice induced severe developmental phenotypes including a thinned cerebral cortex, hydrocephalus, missing cerebellar layering, and non-proliferative cell accumulations in brain stem and cerebellum. An additional homozygous loss of SMARCA4 even resulted in prenatal death for most mice. Interestingly, Blbp-cre::Ctnnb1(ex3)fl/wt::Smarca4fl/fl mutants developed big proliferative lesions in the cerebellum that evolved from E13.5 to E16.5. Histological and molecular analysis of these lesions by DNA methylation analysis and single-cell RNA sequencing suggest an origin in early undifferentiated SOX2-positive cerebellar progenitors. Furthermore, upregulation of WNT signaling and altered actin/cytoskeleton organization and neuronal differentiation were evident in mutant cells. In vitro, cells harboring alterations in both Ctnnb1 and Smarca4 were negatively selected and did not show tumorigenic potential after transplantation in adult recipient mice. However, mutant cells displayed increased proliferation compared to controls in cerebellar explant culture, indicating an important role of the embryonic microenvironment in the development of lesions. Altogether, these results represent an important first step in unravelling tumorigenic mechanisms induced by aberrant WNT signaling and a SMARCA4 deficiency.
2024-04-17 | GSE240627 | GEO
Project description:SMARCA4 gene is mutated in a subset of Group 3 medulloblastomas. ShRNA mediated downregulation of SMARCA4 expression in three Group 3 medulloblastoma cell lines upregulated the expression of myogenic/muscle differentiation related genes as studied by the transcriptome analysis.
2023-03-10 | GSE198463 | GEO
Project description:Almost all medulloblastomas (MB) of the Wingless/Int-1 (WNT) type are characterized by hotspot mutations in CTNNB1, and mouse models have convincingly demonstrated the tumor-initiating role of these mutations. Additional alterations in SMARCA4 are detected in around 20% of WNT MB, but their functional role is mostly unknown. We therefore amended previously described Blbp cre::Ctnnb1(ex3)fl/wt mice by the introduction of a floxed Smarca4 allele. Unexpectedly, mutated β-catenin on its own induced severe developmental phenotypes in Blbp cre::Ctnnb1(ex3)fl/wt mice in our hands, including a thinned cerebral cortex, hydrocephalus, missing cerebellar layering, and non-proliferative cell accumulations in the brain stem and cerebellum. An additional loss of SMARCA4 even resulted in prenatal death for most mice. Respective Blbp cre::Ctnnb1(ex3)fl/wt::Smarca4fl/fl mutants developed large proliferative lesions in the cerebellum evolving from E13.5 to E16.5. Histological and molecular analysis of these lesions by DNA methylation profiling and single-cell RNA sequencing suggested an origin in early undifferentiated SOX2-positive cerebellar progenitors. Furthermore, upregulated WNT signaling, altered actin/cytoskeleton organization, and reduced neuronal differentiation were evident in mutant cells. In vitro, cells harboring alterations in both Ctnnb1 and Smarca4 were negatively selected and did not show tumorigenic potential after transplantation in adult recipient mice. However, in cerebellar explant cultures, mutant cells displayed significantly increased proliferation, suggesting an important role of the embryonic microenvironment in the development of lesions. Altogether, these results represent an important first step towards the unravelling of tumorigenic mechanisms induced by aberrant WNT signaling and SMARCA4 deficiency.
2024-04-17 | GSE241018 | GEO
Project description:AMBRA1 interaction mapping in ATRT cellular model to identify potential interaction partners. BT12, BT16, CHLA06 and CHLA266 were used as cellular model. following AP data were analyzed using DIA-NN and interactions were scored against empty FLAG results.
2023-10-10 | PXD043369 | Pride
Project description:Clinical and molecular risk factors were analyzed in a large cohort of patients with Atypical Teratoid Rhabdoid Tumors (ATRT) recruited to the European Rhabdoid Regsitry (EU-RHAB) and data were validated in a second independent cohort of ATRT patients.
2020-01-31 | GSE141039 | GEO