CPI-17 Overexpression and Its Correlation With the NF2 Mutation Spectrum in Sporadic Vestibular Schwannomas

CPI-17 Overexpression and Its Correlation With the NF2 Mutation Spectrum in Sporadic Vestibular Schwannomas: 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.