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Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated [Multiome]

ABSTRACT: Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated [Multiome]

PROVIDER: PRJNA997825 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25396516_1.fastq.gz	Fastqsanger.gz
	SRR25396516_2.fastq.gz	Fastqsanger.gz
	SRR25396517_1.fastq.gz	Fastqsanger.gz
	SRR25396517_2.fastq.gz	Fastqsanger.gz
	SRR25396518_1.fastq.gz	Fastqsanger.gz

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Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated [Multiome]

Project description:The transcription factor FOXR2 is the universal driver of childhood central nervous system neuroblastoma, FOXR2 activated (NB-FOXR2). NB-FOXR2 tumors arise exclusively in the brain hemispheres, and despite morphological similarities to other pediatric brain tumors, they are a molecularly distinct entity based on DNA methylation profiling. The cell-of-origin is unknown. Here, we profiled a cohort of rare NB-FOXR2 tumors by bulk and single-cell transcriptomics. Through systematic comparative analyses, we delineate tumor transcriptional states and candidate cell-of-origin. More broadly, we demonstrate systematic molecular profiling of childhood cancers to orient oncogenic targeting for in vivo modeling, a critical resource for the study of rare tumors and development of therapeutics.

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Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated [RNA-seq]

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Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated

Project description:Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated

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Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated [RNA-seq]

Project description:Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated [RNA-seq]

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Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated [CUT&RUN]

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Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated

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FOXR2 stabilizes MYCN protein and identifies non-MYCN-amplified neuroblastoma patients with unfavorable outcome

Project description:The stabilization of MYCN by FOXR2 represents an alternative mechanism to MYCN amplification to increase MYCN protein levels. As such, FOXR2 expression identifies another subset of neuroblastoma patients with unfavorable clinical outcome. Background: Clinical outcomes of neuroblastoma patients range from spontaneous tumor regression to fatality. Hence, understanding the mechanisms that cause tumor progression are crucial for the treatment of patients. In this study, we show that FOXR2 activation identifies a subset of neuroblastoma tumors with unfavorable outcome and we investigate the mechanism how FOXR2 relates to poor outcome in patients.

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Project description:Primitive neuroectodermal tumors of the central nervous system (CNS PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children. Using DNA methylation and gene expression profiling we have demonstrated that a significant proportion of institutionally diagnosed CNS PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumor entities, facilitating diagnosis and appropiate therapy for children with these tumors. From the remaining fraction of CNS PNETs, we have identified four distinct new CNS tumor entities extending to other neuroepithelial tumors, each associated with a recurrent genetic alteration and particular histopathological and clinical features. These molecular entities, designated âCNS Neuroblastoma with FOXR2 activation (CNS NB FOXR2)â, âCNS Ewing sarcoma family tumor with CIC alteration (CNS EFT CIC)â, âCNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET MN1)â, and âCNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET BCOR)â, will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by these poorly differentiated CNS tumors. 182 brain tumor samples were selected for RNA extraction and hybridization on Affymetrix Affymetrix Human Genome U133 Plus 2.0 Arrays.

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Project description:Primitive neuroectodermal tumours of the central nervous system (CNS PNETs) are highly aggressive, poorly differentiated embryonal tumours occurring predominantly in young children. Using DNA methylation and gene expression profiling we have demonstrated that a significant proportion of institutionally diagnosed CNS PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumour entities, facilitating diagnosis and appropiate therapy for children with these tumours. From the remaining fraction of CNS PNETs, we have identified four distinct new CNS tumour entities extending to other neuroepithelial tumours, each associated with a recurrent genetic alteration and particular histopathological and clinical features. These molecular entities, designated â??CNS Neuroblastoma with FOXR2 activation (CNS NB FOXR2)â??, â??CNS Ewing sarcoma family tumour with CIC alteration (CNS EFT CIC)â??, â??CNS high grade neuroepithelial tumour with MN1 alteration (CNS HGNET MN1)â??, and â??CNS high grade neuroepithelial tumour with BCOR alteration (CNS HGNET BCOR)â??, will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by these poorly differentiated CNS tumours. 586 brain tumor samples were profiled using the Illumina HumanMethylation450 BeadChip (450k) array.

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