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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

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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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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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Comparison of CGD transgene-expressing and non-expressing tumor cells from a MPNST allograft model

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.

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