CPI-17 Overexpression and Its Correlation With the NF2 Mutation Spectrum in Sporadic Vestibular Schwannomas. Issue 1 (January 2020)

• Record Type: Journal Article
• Authors: Xu, Jianhui; Zhang, Yang; Shi, Yuxuan; Yin, Dongming; Dai, Peidong; Zhao, Weidong; Zhang, Tianyu
• Is Part Of: Otology & neurotology. Volume 41:Issue 1(2020)
• Publication Date: 2020-01
• Subjects: CPI-17 -- NF2 -- Sporadic vestibular schwannoma; Otology -- Periodicals; Ear -- Diseases -- Periodicals; Skull base -- Surgery -- Periodicals; 617.8005
• DOI: 10.1097/MAO.0000000000002430
• Languages: English
• ISSNs: 1531-7129

Abstract

Abstract : Hypothesis: We hypothesized that CPI-17 expression and NF2 mutations are correlated with merlin phosphorylation in the etiology of sporadic vestibular schwannoma (VS). Background: NF2 gene mutations have been identified in the majority of sporadic and NF2 -associated schwannomas and NF2 gene mutations have been shown to result in merlin protein phosphorylation. CPI-17 can drive Ras activity and promote tumorigenic transformation by inhibiting the tumor suppressor merlin. The aim of this study was to determine the correlation between CPI-17 overexpression and the NF2 mutation spectrum in sporadic VS. Methods: In this study, we measured CPI-17 expression and identified NF2 gene alterations in a series of sporadic VS samples. Freshly frozen tumor and matched peripheral blood leukocytes from 44 individuals with sporadic VS were analyzed using next-generation sequencing and Sanger sequencing. Western blotting was used to determine the level of merlin phosphorylation, and immunohistochemistry and Western blotting were used to measure CPI-17 expression in the sporadic VS samples. CCK-8 and wound-healing assays were used to determine the influence of CPI-17 overexpression on cell proliferation. Results: NF2 mutations were identified in 79.5% of sporadic vestibular schwannomas, with all mutations being exclusively somatic. IHC and WB showed the expression of CPI-17 is upregulated in the sporadic VS. NF2 mutation and CPI-17 are positively correlated with merlin phosphorylation. CPI-17 overexpression induces the proliferation of HEI193 cells. Conclusion: NF2 mutations and CPI-17 expression together induce merlin phosphorylation, which is correlated with the tumorigenesis of sporadic VSs. Abstract : Supplemental Digital Content is available in the text