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Objective: Vestibular schwannomas (VSs) can cause serious neurological defects including hearing loss and facial paralysis. The aim of this study is to identify whether Hippo signaling could be a potential targetable pathway for clinical treatment in VSs., Methods: Gene expression profiling was performed in 10 sporadic VSs and 4 normal nerves to identify aberrant genes expression of the Hippo pathway. Western blotting and immunohistochemical staining were used to examine the expression of Hippo core components in 20 VS samples. Neurofibromatosis type 2 (NF2) gene sequencing was also performed in all tumors using sanger sequencing. Verteporfin, inhibitor of yes-associated protein (YAP)-TEA domain family member, was used to assess the effect of proliferation inhibition in human primary VS cells and RT4-D6P2T cell line., Results: We found 51 differentially expressed genes of the Hippo pathway between VSs and healthy controls. Unsupervised analysis identified the 2 molecular variants that significantly related with distinct NF2 mutation status. The phosphorylation levels of large tumor suppressor 1 and YAP were significantly decreased in NF2-mutated VSs compared with wild-type VSs and normal nerves. Immunohistochemical staining showed that increased nuclear YAP expression in VSs was positively correlated with high Ki-67 index and low Merlin expression. Verteporfin reduced viability of primary VS cells and RT4-D6P2T cells., Conclusions: Our findings implicate that deregulation of the Hippo pathway as a molecular mechanism of pathogenesis in human VSs, and suggest inhibition of this pathway as a potential treatment strategy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate 10 candidate single nucleotide polymorphisms (SNPs) in 5 genes (CASP8, XRCC1, WRN, NF2, and BRIP1) to confirm the association between the 5 genes and the meningioma risk in a Chinese population., Methods: We examined 10 candidate SNPs in 5 genes (CASP8, XRCC1, WRN, NF2, and BRIP1) to confirm the association between the 5 genes and the meningioma risk and tumor-related phenotype in 433 individuals, including 215 patients with meningioma and 218 controls., Results: The polymorphisms rs4968451T>G in BRIP1 were significantly associated with the risk of meningioma (TT vs. TG vs. GG additive, P = 0.005; TT+TG vs. GG dominant, P = 0.015; TT/GT+GG recessive, P = 0.034). The significant association was found only in females for BRIP1 rs4968451T>G (TT+TG vs. GG dominant, P = 0.001; TT/GT+GG recessive, P = 0.044). We observed no significant association between genotypes and the meningioma risk for the other 9 SNPs. Through genotype-phenotype analysis, the genotype of BRIP1 rs4968451T>G was also strongly associated with tumor-related phenotypes, including the tumor grade and tumor subtypes. BRIP1 rs4968451T>G was associated with markedly grade I meningioma risk (TT+TG vs. GG dominant, P = 0.008; TT/GT+GG recessive, P = 0.020). In addition, BRIP1 rs4968451T>G was associated with markedly meningothelial and transitional meningioma risk. Furthermore, the genotype of CAPS8, XRCC1, and NF2 was associated with different subtype of meningioma risk., Conclusions: This study indicated a role for BRIP1 gene variations in meningioma and may be informative for future genetic or biological studies of meningioma. These findings will assist in further understanding the genetic cause for meningiomas and guide more effective biological interventions to facilitate meningiomas., (Copyright © 2018. Published by Elsevier Inc.)

Objective: Neurofibromatosis type 2 (NF2) is a common neurocutaneous disorder that exhibits an autosomal dominant inheritance, with a mutation at chromosome 22q12.2. Two forms can be distinguished: the Wishart-phenotype with an early and aggressive course and the Feiling-Gardner-phenotype with a less dramatic presentation. In general, patients present bilateral vestibular schwannomas, meningiomas and neurinomas of the central and peripheral nervous system as well as neurofibromas and gliomas. There is no reported case of pulmonary meningiomas and neurinomas associated with NF2 until now., Patient and Methods: Here, we present a 16-year-old girl with NF-2 associated to CNS and pulmonary tumours and we discuss the case in the backlight of the literature., Results: The reported patient presented a de novo NF2 germline mutation (R341X) and displayed the Wishart-type of NF-2 since she is 11 years old, with a huge anaplastic biparietal falx meningioma and a tentorium meningioma and a tumour-associated parietal mass as well as hypacusis starting at the infant age of 3 years. Multiple cranial and spinal tumours with extra- and intramedullary localization were also found. Moreover, recurrent pulmonary tumours developed and were classified as benign meningiomas and a single neurinoma. No direct evidence concerning a relationship between the pulmonary and cerebral tumours could be drawn., Conclusion: This rare case extends our knowledge of NF2 and also raises interesting questions about the pathogenesis of meningiomas outside the CNS.