PRC2 is a tumor suppressor in malignant peripheral nerve sheath tumor (MPNST)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE226980 | GEO | 2024/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:Comparison of copy number changes in MPNST samples against benign neurofibromas in NF1 patients 24 MPNSTs and 3 NF samples were hybridised to the human 32K BAC tiling path array
2010-05-18 | E-GEOD-16041 | biostudies-arrayexpress
Project description:Comparison of copy number changes in MPNST samples against benign neurofibromas in NF1 patients
2009-05-20 | GSE16041 | GEO
Project description:PRC2 loss of function occurs frequently in human MPNST. Here, we found that PRC2-loss tumors are separated from PRC2-wt ones at the transcriptome level by RNA-seq among 41 human MPNST tumor tissues.
2022-08-17 | GSE206527 | GEO
Project description:Background: Malignant peripheral nerve sheath tumors (MPNST) are soft-tissue sarcomas that can arise either sporadically or in association with neurofibromatosis type 1 (NF1). These aggressive malignancies confer poor survival, with no effective therapy available. Methods: We generated five patient-derived MPNST orthoxenograft models (three NF1-related and two sporadic) and performed an exhaustive histological and molecular characterization of primary MPNSTs and their corresponding orthoxenografts. Finally, orthoxenografts models were used as an in vivo pre-clinical platform to test several treatment strategies. Results: MPNST orthoxenografts recapitulate the histopathological properties and preserve the genomic and transcriptomic status of their parental primary tumors. Additionally, they mimic distal dissemination properties in mice. Compatible with an origin in a catastrophic event and subsequent stabilization, MPNSTs contained highly altered genomes that remained remarkably stable in orthoxenograft establishment and along passages. Although preliminary, the results presented here point to clear differences between NF1-associated and sporadic MPNSTs. In accordance, mutation frequency in sporadic MPNSTs was an order of magnitude higher than in NF1-associated MPNSTs and unsupervised cluster analysis and principal component analysis (PCA) using a MPNST signature perfectly divided the samples between NF1 and sporadic MPNST. Finally, different therapeutic approaches tested in the validated orthoxenograft MPNST models, reveal that sorafenib, or in combination with doxorubicin or rapamycin caused a great tumor reduction in all models. Conclusion: The development of a well-characterized and standardized preclinical model for MPNSTs has laid the foundations for evaluating novel therapeutic strategies in the clinical setting. Moreover, results obtained strongly support the clinical evaluation of Sorafenib in this subset of patients. Primary MPNSTs were implanted in the sciatic nerve of nude mices to create orthoxenograft MPNST models. Several orthoxenograft passages were created. The primary tumor (when available) and passages 1 and 4 were selected for gene expression profiling to demonstrate that the orthoxenografts closely resemble their primary tumors and are stable along xenograft passages.
2015-04-15 | E-GEOD-60082 | biostudies-arrayexpress
Project description:Neurofibromatosis type 1 (NF1) is the most common tumor predisposition syndrome, and is associated with an aggressive soft-tissue sarcoma, malignant peripheral nerve sheath tumours (MPNSTs), the greatest cause of morbidity and mortality in people with NF1. The only potentially curative therapy involves surgery which is not always possible. Even therapy with curative intent is associated with poor overall survival for both sporadic and NF1-related MPNSTs. The development of novel therapies has been largely hindered by a lack of understanding of the molecular events underpinning MPNST pathogenesis. This is a comprehensive multi-omic study of MPNST evolution based on whole genome sequencing and transcriptomic data.
| EGAS00001006069 | EGA
Project description:Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma. Comprehensive proteomic profiles of 23 MPNST tumor specimens were obtained using LC-MS/MS. Among 23 tumor specimens, 13 patients showed favorable prognosis and 10 did local recurrence/distant metastasis.
2022-12-22 | PXD030585 | JPOST Repository
Project description:Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of premature death for patients with Neurofibromatosis type 1 and no approved targeted therapies are available. Transformation from Nf1-null benign plexiform neurofibromas is driven by the loss of the Cdkn2a (Arf) locus. Here, genetically engineered mouse models with combined Nf1 flox/flox and Arf flox/flox alleles were used (crossed with Postn-Cre+ mice). Tissue from MPNSTs that form in the Nf1-/-;Arf-/- setting were used for mRNA sequencing and compared to benign plexiform neurofibroma tissue (Nf1-/- from Nf1 flox/flox; Postn-Cre+ mice, GSE213789) to identify transcriptome signatures from MPNST and compare them to benign plexiform neurofibroma.
2023-12-12 | GSE232707 | GEO
Project description:Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas developed from Schwann cell lineage. They account for up to 10% of all soft tissue sarcomas. Although there is an unmet need for new therapeutic agents for MPNSTs, to date there have been few transcriptomic analyses of this tumor type. We studied FDA approved drugs for MPNST treatment and compared their transcriptomic changes in cell lines before and after treatment. We demonstrated that Fludarabine treated NF1 MPNST cells exhibited altered signaling pathways such as the upregulation of the Wnt/Ca+ pathway and downregulation of the hedgehog and hypoxia signaling pathways in the Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA) analysis. The combined Colchicine and Fludarabine treatment enhanced the cytotoxicity of sporadic MPNST cells through altered signaling pathways, including increased Wnt/β-catenin pathway and others. The transcriptomic analysis comparing NF1/sporadic MPNST cells and normal Schwann cells indicated that NF1 MPNST cells had more splicing events, fewer single nucleotide variants, and induced RNA expression than sporadic MPNST cells. In summary, we identified a transcriptomic differences between MPNSTs and Schwann cells, between sporadic MPNST cells and NF1 MPNST cells, and between drug treated MPNST cells and vehicle treated cells.
2023-10-21 | GSE159896 | GEO
Project description:Background: Malignant peripheral nerve sheath tumors (MPNST) are soft-tissue sarcomas that can arise either sporadically or in association with neurofibromatosis type 1 (NF1). These aggressive malignancies confer poor survival, with no effective therapy available. Methods: We generated five patient-derived MPNST orthoxenograft models (three NF1-related and two sporadic) and performed an exhaustive histological and molecular characterization of primary MPNSTs and their corresponding orthoxenografts. Finally, orthoxenografts models were used as an in vivo pre-clinical platform to test several treatment strategies. Results: MPNST orthoxenografts recapitulate the histopathological properties and preserve the genomic and transcriptomic status of their parental primary tumors. Additionally, they mimic distal dissemination properties in mice. Compatible with an origin in a catastrophic event and subsequent stabilization, MPNSTs contained highly altered genomes that remained remarkably stable in orthoxenograft establishment and along passages. Although preliminary, the results presented here point to clear differences between NF1-associated and sporadic MPNSTs. In accordance, mutation frequency in sporadic MPNSTs was an order of magnitude higher than in NF1-associated MPNSTs and unsupervised cluster analysis and principal component analysis (PCA) using a MPNST signature perfectly divided the samples between NF1 and sporadic MPNST. Finally, different therapeutic approaches tested in the validated orthoxenograft MPNST models, reveal that sorafenib, or in combination with doxorubicin or rapamycin caused a great tumor reduction in all models. Conclusion: The development of a well-characterized and standardized preclinical model for MPNSTs has laid the foundations for evaluating novel therapeutic strategies in the clinical setting. Moreover, results obtained strongly support the clinical evaluation of Sorafenib in this subset of patients.
2015-04-15 | GSE60082 | GEO
Project description:The diagnosis of Malignant peripheral nerve sheath tumors (MPNSTs) can be challenging, but is aided by their characteristic DNA methylation profile (DMP). An MPNST-like group, characterized by retained H3K27me3 expression, was recently recognized. To evaluate the diagnostic usefulness of DMP in pediatric/juvenile MPNSTs, we selected pediatric/juvenile malignancies from the Bambino Gesù Children's Hospital DMP database. DMP revealed unexpected molecular heterogeneity in histologically homogenous MPNSTs/Atypical neurofibromas, while samples with MPNST-like DMP manifested histological diversity. In conclusion, DMP is useful in diagnosing MPNST, discriminating morphologic mimics classified as MPNST in premolecular era, and investigating the MPNST-like ‘hybrid’ group in pediatrics.
2024-01-29 | GSE246644 | GEO