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.
Project description:We performed a genome-wide CRISPRi screen to identify potential contributors to radioresistance in the JH02.2 malignant peripheral nerve sheath tumor (MPNST) cell line.
Project description:We used single-cell RNA-sequencing (scRNA-seq) to study the effect of ionizing radiation on the transcriptomes of malignant peripheral nerve sheath tumors (MPNSTs) in vivo and in the context of the innate and adaptive immune response.
Project description:Malignant peripheral nerve sheath tumors (MPNSTs) are deadly sarcomas that lack effective therapies. In most MPNSTs, the retinoblastoma (RB1) tumor suppressor is disabled by hyperactivation of cyclin dependent kinases (CDKs), commonly through loss of CDK inhibitory proteins such as p27(Kip1). RABL6A is an inhibitor of RB1 whose role in MPNSTs is unknown. To gain insight into MPNST development and establish new treatment options, we investigated RABL6A-RB1 signaling and CDK inhibitor-based therapy in MPNSTs.
Project description:The clinical significance of specific genetic alterations, methylation signatures or microenvironmental composition in malignant peripheral nerve sheath tumors (MPNSTs) is unclear. We assembled an updated cohort of 30 patients with MPNSTs treated with surgical resection and postoperative radiation who underwent methylation profiling and detailed clinical follow-up. The data included in this submission include 7 of 30 samples, the remainder of which were submitted separately under GSE212963.
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. Benign plexiform neurofibromas have been successfully treated with selumetinib, a MEK inhibitor, but after progression to MPNST, MEK inhibition alone is not effective. Frequently, adaptive responses to single agent targeted inhibitors invokes alterations in receptor tyrosine kinase expression and feedback regulation that leads to inhibitor bypass. Here, the effects of SHP099, an inhibitor of the protein-tyrosine phosphatase SHP2 (encoded by the PTPN11 gene) was tested alone and in combination with trametinib (MEKi) in an NF1 MPNST patient derived xenograft model (PDX4) treated with SHP099, hydroxychloroquine (HCQ) or the combination. Kinase enrichment proteomic analysis was performed using tumor tissue treated with SHP099, hydroxychloroquine (HCQ) or the combination to evaluate the effects on the functional kinome.