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NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors

ABSTRACT: NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors

PROVIDER: PRJNA1050208 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27147016_1.fastq.gz	Fastqsanger.gz
	SRR27147016_2.fastq.gz	Fastqsanger.gz
	SRR27147017_1.fastq.gz	Fastqsanger.gz
	SRR27147017_2.fastq.gz	Fastqsanger.gz
	SRR27147018_1.fastq.gz	Fastqsanger.gz

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NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors (RNA-Seq)

Project description:The pathogenesis of many rare tumor types is poorly understood, preventing the design of effective treatments. Solitary Fibrous Tumors (SFTs) are neoplasms of mesenchymal origin that affect 1/1,000,000 individuals every year and are clinically assimilated to sarcomas. SFTs are commonly found throughout the body and can be surgically removed upon diagnosis. However, 30-40% of tumors become aggressive and can locally relapse or metastasize. There are no effective treatments for malignant SFTs to date. The molecular hallmark of SFTs is a gene fusion between the NAB2 and STAT6 loci on chromosome 12, resulting in a chimeric protein of poorly characterized function called NAB2-STAT6. We use primary samples and an inducible cell model to discover that NAB2-STAT6 operates as a transcriptional coactivator for a specific set of enhancers and promoters that are normally targeted by the EGR1 transcription factor. In physiological conditions, NAB2 is primarily localized to the cytoplasm and only a small nuclear fraction is available to operate as a co-activator of EGR1 targets. NAB2-STAT6 redirects NAB1, NAB2, and additional EGR1 to the nucleus and bolster the expression of neuronal EGR1 targets. The STAT6 moiety of the fusion protein is a major driver of its nuclear localization and further contributes to NAB2’s co-activating abilities. In primary tumors, NAB2-STAT6 activates a neuroendocrine gene signature that sets it apart from most sarcomas. These discoveries provide new insight into the pathogenesis of SFTs and reveal new targets with therapeutic potential.

2024-05-01 | GSE249702 | GEO

NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors (ChIP-Seq)

2024-05-01 | GSE249701 | GEO

NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors (ATAC-Seq)

2024-05-01 | GSE249700 | GEO

NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors (RNA-Seq)

Project description:NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors (RNA-Seq)

| PRJNA1050217 | ENA

NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors (ATAC-Seq)

Project description:NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors (ATAC-Seq)

| PRJNA1050213 | ENA

NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors (ChIP-Seq)

Project description:NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors (ChIP-Seq)

| PRJNA1050212 | ENA

NAB2-STAT6 Gene Fusions in Solitary Fibrous Tumor by Integrative Sequencing

Project description:<p>Transcriptome sequencing of solitary fibrous tumors / hemangiopericytomas from a variety of anatomic sites revealed recurrent gene fusions between two genes, NAB2 and STAT6. All SFTs examined exhibited an in-frame fusion transcript encoding a fusion protein containing the EGR1 interaction domain of NAB2 with the transcriptional activation domain of STAT6. Functional testing of the fusion alleles confirmed the conversion of the wt NAB2 repressor into a transcriptional activator. A range of individual fusion junctions can be detected by next-generation sequencing acro the sample set, highlighting the suitability of this method in the diagnostic characterization of SFTs. This study indentified the pathognomonic alteration in solitary fibrous tumors and illuminates a pathway towards targeted therapeutics for this cancer.</p>

| phs000567 | dbGaP

Identification of Recurrent NAB2-STAT6 Gene Fusions in Solitary Fibrous Tumor by Integrative Sequencing

| phs000567.v1.p1 | EGA

NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-05-01 | GSE249703 | GEO

Solitary Fibrous Tumours gene profiling study

Project description:Using whole-genome DNA microarrays, we defined the gene expression profiles of 16 Solitary Fibrous Tumours (SFT) and haemangiopericytomas (HPC) (9 HPC and 7 SFT). Expression profiles were compared to publicly available expression profiles of additional SFT or HPC, meningiomas and synovial sarcomas.

2023-02-08 | E-MTAB-11447 | biostudies-arrayexpress

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