E6637050-d810-4d8a-b939-d0f4aaf0fc0d - samples
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PROVIDER: EGAD00001008608 | EGA |
REPOSITORIES: EGA
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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:The purpose of this study is to identify expression differences between untreated and Doxycycline treated human malignant peripheral nerve sheathing tumors (MPNST) cell lines. We sequenced mRNA from 6 lentiviral infected MPNST human stable cell lines(STS26T-pLIX405-KANK1 using Illumina Hiseq 2500 sequencing platform. Three control samples are untreated stable cells and three samples are Doxycycline treated (1 ug/ml).
2017-01-12 | GSE85271 | GEO
Project description:Neurofibromatosis Type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating effects of hyperactive Ras in NF1 tumors are unknown. Cross-species transcriptome analyses of mouse and human neurofibromas and MPNSTs identified global negative feedback of genes that regulate Ras-Raf- MEK- extracellular signal-regulated protein kinase (ERK) signaling in both species. Nonetheless, activation of ERK was sustained in mouse and human neurofibromas and MPNST. PD0325901, a highly selective pharmacological inhibitor of MEK, was used to test whether sustained Ras-Raf-MEK-ERK signaling contributes to neurofibroma growth in the Nf1fl/fl;Dhh-cre mouse model or in NF1 patient MPNST cell xenografts. PD0325901 treatment reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of mice implanted with human MPNST cells, and shrank neurofibromas in >80% of mice tested. PD0325901 also caused effects on tumor vasculature. Our data demonstrate that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide strong rationale for testing MEK inhibitors in NF1 clinical trials. 83 microarrays: Mouse control (15), Mouse neurofibroma (15), Mouse MPNST (18); Human nerve (3), Human neurofibroma (26), Human MPNST (6) We used the same human tumor samples as in series GSE14038 (dNF, pNF and MPNST). However, instead of referencing gene expression changes to the normal human Schwann cell samples (NHSC) as we did in series GSE14038, we generated three (new) normal nerve samples (samples jan-N1-3) and referenced gene expression changes to those samples. Moreover, the analysis of series GSE14038 evaluated changes in expression between NHSC, benign tumor subtypes (dNF and pNF), and malignant tumors (MPNST), while our present submission evaluated changes between normal nerve, benign tumors (combined dNF and pNF),and malignant tumors (MPNST). The Series supplementary 'merged_data.txt' file contains the data for 9,891 transcripts that were statistically different in at least one of the two species and present in both mouse and human data sets.
2012-12-28 | E-GEOD-41747 | biostudies-arrayexpress
Project description:NF1-associated malignant peripheral nerve sheath tumors (MPNST) are the major cause of mortality in neurofibromatosis. MPNST arise from benign peripheral nerve plexiform neurofibromas (PN) which originate in the embryonic neural crest cell lineage. Using reporter transgenes that label early neural crest lineage cells in multiple NF1 MPNST mouse models, we discovered and characterized a rare MPNST cell population with stem cell-like properties that is essential for tumor initiation and relapse. Following isolation of these cells we derive a cancer stem cell specific gene expression signature that includes consensus embryonic neural crest genes and we also identify Nestin as a novel marker for the MPNST cell of origin. Finally, application of the mouse cancer stem cell signature to single cell sequencing data from a rare NF1-associated MPNST precursors called atypical neurofibromatosis neoplasms of uncertain biologic potential (ANNUBP), identifies preformed unsupervised gene expression cell clusters. Enrichment of the cancer stem cell signature in cognate human tumors supports the generality and relevance of cancer stem cells to therapy development.
2021-04-07 | GSE165826 | GEO
Project description:We devised a transgene that expresses in the neural crest lineage cells at embryonic stage day 13.5. The transgene has an inducible Cre cassette and was used to induce Trp53 and Nf1 gene recombination in the cells of dorsal root ganglia and boundary cap of nerve roots (DRG&BC) at E13.5. The malignant peripheral nerve sheath tumor (MPNST) allograft model was generated by sciatic nerve injection using the recombined E13.5 DRG&BC cells. The nuclear localized eGFP from the transgene was used to facilitate the florescence activated cell sorting (FACS) of GFP+ and GFP- tumor cells after removal of wildtype cells from the dissociated tumors, including immune cells, endothelia cells and blood cells. GFP+ and GFP- tumor cells were harvested from 5 different allograft MPNSTs. Total RNA were prepared from 10 samples were sequenced on Hiseq4000 sequencer. The data was to support the transgene-labeled cancer stem cell population in MPNST mouse models.
2021-01-31 | GSE152752 | GEO
Project description:Understanding biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumors is essential, as tumor biomarkers, prognostic factors and therapeutics are all lacking. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n = 10), NF1-derived primary benign neurofibroma Schwann cells (n = 22), malignant peripheral nerve sheath tumor (MPNST) cell lines (n = 13), benign neurofibromas (n = 26) and MPNST (n = 6). Dermal and plexiform neurofibromas were indistinguishable. A prominent theme in the analysis was aberrant differentiation. Neurofibromas repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes upregulated in the sarcomas were significantly enriched for genes activated in neural crest cells. We validated differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in neurofibroma and MPSNT tissue sections and targeting SOX9 - strongly expressed in NF1-related tumors - caused MPNST cell death. SOX9 is a biomarker of neurofibroma and MPNST, and possibly a therapeutic target in NF1. Keywords: tumor stage 86 microarrays, consisting of 77 samples and 9 batch reference samples: NHSC (10), dNFSC (11), pNFSC (11), MPNST cell lines (13), dNF (13), pNF (13), MPNST (6)
2009-07-15 | E-GEOD-14038 | biostudies-arrayexpress
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
Project description:Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma that lacks effective therapeutic strategies. By characterizing recurrent gene copy number aberrations, we gain insight into the most altered pathways with the purpose of scanning possible therapeutic targets. We conducted a microarray-based comparative genomic hybridization profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Cancer Hospital. All samples had at least 90% tumor content. Commercially available normal genomic DNAs were used as control.
2011-11-26 | E-GEOD-33881 | biostudies-arrayexpress
Project description:Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST‐specific biomarkers for screening patients with NF1. Genome‐wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1‐MPNST cell lines was performed to identify and validate candidate MPNST‐specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST‐specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, cfMBD‐seq was applied to profile the cfDNA methylome of blood from patients with MPNST and NF1. Based on stringent feature‐selection criteria and predictive modeling, we identified 73 candidate MPNST‐specific CpGs (67 with unique CpG island locations) that reliably discriminated MPNSTs from neurofibromas. Validation of five candidate biomarkers confirmed successful MPNST detection (sensitivity: > 88%, specificity: > 91%) in tissues. In plasma samples, 63 of 67 selected genomic regions had greater than 1.2‐fold higher methylation in patients with MPNST than those with NF1. Further, we identified 15 CpG islands that consistently separated plasma from patients with confirmed MPNST diagnosis from plasma of individuals with NF1 without a diagnosis of malignant transformation (FDR < 0.1). Our findings confirmed a unique hypermethylation pattern present during malignant transformation. This study highlights the potential to be further investigated further as biomarkers in clinical settings for early MPNST detection in patients with NF1.
2024-11-25 | GSE282216 | GEO
Project description:Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, cfMBD-seq was applied to profile the cfDNA methylome of blood from patients with MPNST and NF1. Based on stringent feature-selection criteria and predictive modeling, we identified 73 candidate MPNST-specific CpGs (67 with unique CpG island locations) that reliably discriminated MPNSTs from neurofibromas. Validation of five candidate biomarkers confirmed successful MPNST detection (sensitivity: > 88%, specificity: > 91%) in tissues. In plasma samples, 63 of 67 selected genomic regions had greater than 1.2-fold higher methylation in patients with MPNST than those with NF1. Further, we identified 15 CpG islands that consistently separated plasma from patients with confirmed MPNST diagnosis from plasma of individuals with NF1 without a diagnosis of malignant transformation (FDR < 0.1). Our findings confirmed a unique hypermethylation pattern present during malignant transformation. This study highlights the potential to be further investigated as biomarkers in clinical settings for early MPNST detection in patients with NF1.
2024-12-19 | GSE280335 | GEO