Identifying transcriptomic pathways mediating radiotherapy response in malignant peripheral nerve sheath tumors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE290674 | GEO | 2025/03/29
REPOSITORIES: GEO
Similar Datasets
Project description:Identifying transcriptomic pathways mediating radiotherapy response in malignant peripheral nerve sheath tumors
| PRJNA1229519 | ENA
Project description:We established a new genetically engineered mouse (GEM) model of malignant peripheral nerve sheath tumors (MPNST) based on postnatal deletion of a Nf1;Trp53 cis-conditional allele by the tamoxifen-inducible Plp-CreER (NP-Plp). We also generated two Lats1;2 conditional knockout models by using Nestin-Cre (Lats-Nes) and Plp-CreER (Lats-Plp), both of which also develop tumors similar to MPNST (GEM-PNST). To evaluate these models, transcriptome analyses were performed to compare these models and with human MPNST, plexiform neurofibromas (PNF), and neurofibromas (NF).
2024-03-24 | GSE172221 | GEO
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: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: Conditionally replicative adenoviruses (CRAds) preferentially infect and lyse tumor cells. While CRAds have been clinically applied, their potential for neurofibromatosis type-1 associated malignant peripheral nerve sheath tumors (MPNSTs) remains unexplored. This study evaluates Cyclooxygenase 2 (COX2)-driven CRAds as a therapy for MPNST. METHODS: Viruses with wild type (WT) and modified fiber-knob domains were assessed for binding efficiency to the MPNST models. Viral infectivity, spread, and susceptibility of MPNST cells to oncolytic adenoviruses were assessed using both WT viruses or engineered CRAd constructs, with cell viability quantification. Tumor growth rates and survival probability of mice bearing human tumor xenografts or syngeneic allografts were assessed using intratumoral injections of CRAds. RESULTS: RGD-modified fibers exhibited improved binding to MPNST cells compared to non-cancer Schwann cells. vectors effectively replicated and lysed MPNST cells, displaying enhanced selectivity towards transformed cells. Tumor-bearing immunodeficient mice survived significantly longer when injected with CRAds compared to PBS controls, and immunocompetent models demonstrate robust infiltration of CD8+ T-cells. CONCLUSIONS: CRAds demonstrate selective binding and efficient replication in MPNST cells, leading to tumor cell lysis while sparing non-cancerous cells. These results suggest that oncolytic adenoviruses may have the potential as novel agents for MPNST therapy and thus warrant further investigation.
2024-04-24 | GSE246610 | GEO
Project description:Malignant peripheral nerve sheath tumors (MPNST) are aggressive cancers that occur spontaneously (sporadic MPNST) or from pre-existing, benign plexiform neurofibromas in neurofibromatosis type 1 (NF1) patients. MPNSTs metastasize easily, are resistant to therapeutic intervention and are frequently fatal. The molecular changes underlying the transition to malignancy in the NF1 setting are incompletely understood. Here we investigate the involvement of microRNAs in this process. Using an RT-PCR platform microRNA expression profiles were determined from a unique series of archival paired samples of plexiform neurofibroma and MPNST. At least 90 differentially expressed microRNAs (p<0.025; FDR<10%) were identified between the paired samples. Most microRNAs (91%) were found downregulated and 9% of the microRNAs were upregulated in MPNST. Based on the fold changes and statistical significance three downregulated microRNAs (let-7b-5p, miR-143-3p, miR-145-5p) and two upregulated microRNAs (miR135b-5p and miR-889-3p) were selected for further functional characterization. Their expression levels were validated in a relevant cell line panel and a series of unpaired fresh frozen tumor samples containing plexiform neurofibromas, atypical neurofibromas and MPNSTs. As part of the validation process we also determined and analyzed microRNA expression profiles of sporadic MPNSTs observing that microRNA expression discriminates NF1-associated and sporadic MPNSTs emphasizing their different etiologies. The involvement of microRNAs in tumorigenesis and cancer progression was examined in NF1-derived MPNST cell lines through modulating microRNA levels by transient transfection of microRNA mimics or inhibitors. The effects of microRNAs on cellular proliferation, migration, invasion and Wnt/ẞ-catenin signaling were determined. Our findings indicate that, some of the selected microRNAs affect migratory and invasive capabilities and Wnt signaling activity. It was observed that the functional effects upon microRNA modulation are distinct in different cell lines. From our study we conclude that miRNAs play essential regulatory roles in MPNST facilitating tumor progression.
2019-11-26 | GSE140986 | GEO
Project description:Plexiform neurofibromas (PNF) are benign peripheral nerve sheath tumors (PNST) that arise in persons with neurofibromatosis type 1 (NF1). Despite similar histological appearance, these neoplasms proceed along diverse evolutionary trajectories, with a subset progressing to a devastating form of sarcoma called malignant peripheral nerve sheath tumor (MPNST), the leading cause of premature death in individuals with NF1. Malignant transformation of PNF often occurs through the development of atypical neurofibroma (ANF) precursor lesions characterized by distinct histopathological features and CDKN2A copy number loss. While genomic studies have improved our understanding of key driver events promoting tumor progression, the transcriptional alterations that precede malignant transformation remain poorly understood. Here we resolve gene expression profiles in PNSTs across the neurofibroma-to-MPNST continuum in NF1 patients and genetically engineered mouse models, providing insight into nascent molecular features associated with neurofibroma evolution and transformation. These findings highlight the need for molecular diagnostic tools that augment conventional histopathological criteria to identify neurofibromas at high risk of undergoing malignant transformation, facilitating risk-adapted care.
2023-12-14 | GSE239561 | GEO
Project description:Aberrant DNA methylation (DNAm) was first linked to cancer over 25 years ago. Since then, many studies have associated hypermethylation of tumour suppressor genes and hypomethylation of oncogenes to the tumourigenic process. However, most of these studies have been limited to the analysis of promoters and CpG islands (CGIs). Recently, new technologies for whole-genome DNAm (methylome) analysis have been developed, enabling unbiased analysis of cancer methylomes. Using MeDIP-seq, we report a sequencing-based comparative methylome analysis of malignant peripheral nerve sheath tumours (MPNST), benign Neurofibromas and normal Schwann cells. Analysis of these methylomes revealed a complex landscape of DNAm alterations. Contrary to the current dogma, significant global hypomethylation was not observed in the MPNST methylome. However, a highly significant (P<10-100) directional difference in DNAm was found in satellite repeats, suggesting these repeats to be the main target for hypomethylation in MPNST. Comparative analysis of the MPNST and Schwann cell methylomes identified 101,466 cancer-associated differentially methylated regions (cDMRs). Analysis showed these cDMRs to be significantly enriched for two satellite repeat types (SATR1 and ARLM-NM-1) and suggests an association between aberrant DNAm of these sequences and transition from healthy cells to malignant disease. Significant enrichment of hypermethylated cDMRs in CGI shores (P<10-60), non-CGI-associated promoters (P<10-4) and hypomethylated cDMRs in SINE repeats (P<10-100) was also identified. Integration of DNAm and gene expression data showed that the expression pattern of genes associated with CGI shore cDMRs was able to discriminate between disease phenotypes. This study establishes MeDIP-seq as an effective method to analyse cancer methylomes. Examination of methylation profiles in malignant, benign and normal tissue
2011-01-01 | E-GEOD-21714 | biostudies-arrayexpress
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