Pathogenic Variants and Allele Loss of the NF2 and LZTR1 Gene in Sporadic Vestibular Schwannoma.

Background/aim: Pathogenic variants and allele-loss of the NF2 gene with Merlin loss as consequence is the driving genetic event for vestibular schwannoma development. Our knowledge about the pathogenic NF2 variants in sporadic vestibular schwannoma is insufficient. Therefore, we analyzed a cohort of sporadic vestibular schwannomas by panel-sequencing.

Patients and methods: Forty-one sporadic vestibular schwannomas from 26 male and 15 female patients were included. DNA from tumor tissues was sequenced with a custom panel for the NF2 and LZTR1 genes. Allele-loss of the NF2 locus was also examined using multiplex-ligation-dependent probe-amplification. These genetic data were correlated with clinical parameters including hearing, tumor extension and growth.

Results: Among the 41 tumor samples, 34 had one pathogenic variant or an allele-loss of NF2 gene and one tumor showed a pathogenic variant in the LZTR1 gene. Allele frequencies of the total of 46 pathogenic variants varied from 0.05 to 0.82, and none of these variants was found in blood. For 6 tumors, no pathogenic variants were found while 4 of them had allele-loss of the NF2 gene. When the tumors were divided into 3 groups according to the counts of inactivating events (pathogenic variants and allele loss), the clinical parameters including hearing, tumor structure in MRI, tumor growth, tumor size and postoperative facial function did not differ significantly.

Conclusion: There was no correlation between phenotype and genetic alterations of the NF2 or LZTR1 gene in sporadic schwannomas. Genetic inactivating events are the precondition for the development of vestibular schwannomas but do not influence their growth and other features.