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Genomic characterization of the MPNST

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33881 | GEO | 2011/11/26

SECONDARY ACCESSION(S): PRJNA148353

REPOSITORIES: GEO

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Genomic characterization of the MPNST

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

Malignant peripheral nerve sheath tumor (MPNST) tumor samples

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2022-12-22 | PXD030585 | JPOST Repository

Profiling the cancer-prone microenvironment in a zebrafish model for MPNST

Project description:Microenvironmental contributions to soft tissue sarcoma progression are relatively undefined, particularly in the context of sarcoma onset. Use of animal models to reveal these contributions is impeded by (1) the difficulty in discriminating between microenvironmental, precancerous, and cancer cells; and (2) the challenge in defining a precancerous microenvironment. We developed a zebrafish model that allows segregation of microenvironmental, precancerous, and cancerous cell populations by fluorescence-activated cell sorting. This model exhibits high predilection for malignant peripheral nerve sheath tumor (MPNST), a type of soft tissue sarcoma that exhibits rapid, aggressive growth. Using RNA-seq, we profiled the transcriptomes of microenvironmental cells from our zebrafish MPNST model. We show broad activation of inflammatory and immune-associated signaling networks and significant upregulation of tumor-promoting ligands in both precancerous and cancerous microenvironments. We also identify specific ligand-receptor pairs that may promote sarcomagenesis. This work provides insight into how the microenvironment may promote MPNST initiation and progression.

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Cdkn2a loss in a model of neurofibroma demonstrates stepwise tumor progression to atypical neurofibroma and MPNST

Project description:Plexiform neurofibromas (PN) are benign nerve sheath Schwann cell tumors, common in patients with neurofibromatosis type 1 (NF1), that are characterized by biallelic mutations in the NF1 tumor suppressor gene. Atypical neurofibromas (ANF) show additional frequent loss of CDKN2A/Ink4a/Arf and may be precursor lesions of aggressive malignant peripheral nerve sheath tumors (MPNST). We combined loss of Nf1 in developing

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Malignant peripheral nerve sheath tumor (MPNST) and MPNST-like entities defined by DNA methylation profile in pediatric and juvenile population

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.

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The histone modification change between PRC2-wt and PRC2-loss in human MPNST cancer cells

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2021-04-07 | GSE165826 | GEO

RNA seq of MPNST tumour samples

Project description:RNA sequencing of 10 MPNST tumour samples as part of a larger study of MPNST. Article: LyskjÃƒÂ¦r et al, 2020, J Pathol, "H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours".

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Transcription profiling of human MPNST cancer cells infected with G207 an oncolytic HSV

Project description:We used microarrays to identify genes regulated during oncolytic HSV infection. Oncolytic herpes simplex viruses (oHSV) are promising anticancer therapeutics. We sought to identify alterations in gene expression during oHSV infection of human cancer cells. Human malignant peripheral nerve sheath tumor (MPNST) cells were infected with G207, an ICP34.5-deleted oHSV previously evaluated in clinical trials. G207-infected cells demonstrated massive degradation of cellular mRNAs, while a subset were upregulated. A gene signature of 21 oHSV-induced genes contained 7 genes known to be HSV-induced. Go ontology classification revealed that a majority of upregulated genes are involved in Jak/STAT signaling, transcriptional regulation, nucleic acid metabolism, protein synthesis and apoptosis. Ingenuity-defined functional networks highlighted nodes for AP-1 subunits and interferon signaling via STAT1, SOCS1, SOCS3 and RANTES. Upregulation of SOCS1 correlated with sensitivity of MPNST lines to G207 and depletion of SOCS1 reduced virus replication >1-log. The transcriptome of oHSV-induced genes may predict oncolytic efficacy and provides rationale for next generation oncolytics. Experiment Overall Design: 5 human MPNST cancer cell lines were infected with G207 or mock infected for 6 hours followed by RNA extraction and hybridization on Affymetrix microarrays.

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