The transcriptomic signature of painful and non-painful human NF2 schwannomas [set1]
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ABSTRACT:
PROVIDER: PRJNA575539 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10220726_1.fastq.gz | Fastqsanger.gz | |||
| SRR10220726_2.fastq.gz | Fastqsanger.gz | |||
| SRR10220727_1.fastq.gz | Fastqsanger.gz | |||
| SRR10220727_2.fastq.gz | Fastqsanger.gz | |||
| SRR10220728_1.fastq.gz | Fastqsanger.gz |
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Project description:Schwannomas are benign peripheral nerve sheath tumors that are associated with substantial morbidity including severe, persistent pain. Treatment, essentially limited to surgical resection, is associated with significant morbidity and for many patient’s efficacious treatment of tumor-related pain is not achievable. There is an urgent need to elucidate the molecular mechanisms underlying schwannoma-induced pain as a first step in development of new therapeutics. In this study, we performed next-generation RNASequencing on a small cohort of formalin fixed paraffin-embedded, painful, and non-painful schwannoma samples obtained from Neurofibromatosis type 2 (NF2) patients. Differential gene and isoform level expression analysis revealed significant transcriptomic differences between painful and non-painful tumors; differentially regulated genes included members of the fibroblast growth factor (FGF) family of genes. Using a xenograft model of human-NF2 we demonstrated that over-expression of FGF7 in schwannoma cells was associated with the development of pain-like behaviors. These results demonstrate both the value of RNASeq utilizing formalin fixed tissues and reveal a novel pathway responsible for neoplasm-associated pain.
2020-05-01 | GSE138344 | GEO
Project description:The transcriptomic signature of painful and non-painful human NF2 schwannomas
| PRJNA575542 | ENA
Project description:The transcriptomic signature of painful and non-painful human NF2 schwannomas [set2]
| PRJNA575540 | ENA
Project description:Schwannomas are benign peripheral nerve sheath tumors that are associated with substantial morbidity including severe, persistent pain. Treatment, essentially limited to surgical resection, is associated with significant morbidity and for many patient’s efficacious treatment of tumor-related pain is not achievable. There is an urgent need to elucidate the molecular mechanisms underlying schwannoma-induced pain as a first step in development of new therapeutics. In this study, we performed next-generation RNASequencing on a small cohort of formalin fixed paraffin-embedded, painful, and non-painful schwannoma samples obtained from Neurofibromatosis type 2 (NF2) patients. Differential gene and isoform level expression analysis revealed significant transcriptomic differences between painful and non-painful tumors; differentially regulated genes included members of the fibroblast growth factor (FGF) family of genes. Using a xenograft model of human-NF2 we demonstrated that over-expression of FGF7 in schwannoma cells was associated with the development of pain-like behaviors. These results demonstrate both the value of RNASeq utilizing formalin fixed tissues and reveal a novel pathway responsible for neoplasm-associated pain.
2020-05-01 | GSE138346 | GEO
Project description:Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them. In order to find target to fight against vestibular schwannoma, we performed an analysis of gene expression by microarrays.
2013-03-01 | E-GEOD-39645 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-05-01 | GSE138347 | GEO
Project description:Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them.
2013-03-01 | GSE39645 | GEO
Project description:Genome-wide DNA methylation profiling of 22 schwannomas belonging to three different genotypes (NF2-mutant, SOX10-mutant, and HTRA1-fused). The Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue of 22 schwannomas.
2023-07-13 | GSE197094 | GEO
Project description:Treatment of multiple intracranial schwannomas in patient with neurofibromatosis type 2 (NF2) is extremely unsatisfactory and innovative therapeutic approaches are urgently needed. The lack of clinically relevant NF2 models has severely hampered drug discovery in this rare disease. Here, we report for the first time the establishment and characterization of patient-derived xenograft (PDX) and cell line models of NF2-associated schwannoma, which retain the gene mutations and transcriptome profile, and recapitulate the morphological and histopathological features with the patient tumors, retain patient NF2 mutations, and maintain gene expression profiles resembling the patient tumor profiles with the preservation of multiple key signaling pathways commonly dysregulated in human schwannoma. Using expression profiling, we found that the PI3K/AKT/mTOR networks are elevated in NF2-associated vestibular schwannomas, as well as in PDX models.
2022-04-04 | GSE180338 | GEO
Project description:Neurofibromatosis type 2 is an inherited neoplastic disease consisting of schwannomas, meningiomas, and ependymomas that is caused by inactivation of the tumor suppressor gene NF2. The NF2 gene product, merlin, has no intrinsic catalytic activity; its tumor suppressor function is mediated through the proteins with which it interacts. However, there is no consensus about which merlin interactions are necessary for tumor suppression. We used proximity biotinylation followed by mass spectrometry and direct binding assays to characterize the proteins that associate with merlin and merlin mutants in immortalized Schwann cells. We identified 52 proteins that associate with merlin, including a previously unreported merlin binding protein, ASPP2. Our results identify merlin as a component of mechanosensing signal transduction pathways in cell junctions, in the context of a specific set of structures and molecules through which it acts, in a cell type relevant to schwannoma formation.
2019-04-25 | PXD012017 | Pride