Transcriptomic signature of painful human neurofibromatosis type 2 schwannomas

Abstract

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.