Abstract
Schwannomas are benign neoplasms that can cause gain- and loss-of-function neurological phenotypes, including severe, intractable pain. To investigate the molecular mechanisms underlying schwannoma-associated pain we compared the RNA sequencing profile of painful and non-painful schwannomas from NF2 patients. Distinct segregation of painful and non-painful tumors by gene expression patterns was observed. Differential expression analysis showed the upregulation of fibroblast growth factor 7 (FGF7) in painful schwannomas. Behavioral support for this finding was observed using a xenograft human NF2-schwannoma model in nude mice. In this model, over-expression of FGF7 in intra-sciatically implanted NF2 tumor cells generated pain behavior compared with controls.
© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Female
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Fibroblast Growth Factor 7 / biosynthesis
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Fibroblast Growth Factor 7 / genetics*
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Humans
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Male
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Mice
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Mice, Nude
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Neurilemmoma / genetics*
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Neurilemmoma / metabolism
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Neurilemmoma / pathology
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Neurofibromatosis 2 / genetics*
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Neurofibromatosis 2 / metabolism
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Neurofibromatosis 2 / pathology
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Pain / genetics*
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Pain / metabolism
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Pain / pathology
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Sciatic Neuropathy / genetics
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Sciatic Neuropathy / metabolism
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Sciatic Neuropathy / pathology
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Sequence Analysis, RNA / methods*
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Transcriptome / genetics*
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Xenograft Model Antitumor Assays / methods
Substances
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Fgf7 protein, mouse
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Fibroblast Growth Factor 7
Grants and funding
This work was funded by Bioinformatics Support Program, Yale School of Medicine; MGH; Molecular Biology Core Facilities; Dana‐Farber Cancer Institute; Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital.