Genomics of vestibular schwannoma

The majority of vestibular schwannomas occur as solitary tumors in otherwise healthy individuals with no family history of vestibular schwannomas, while approximately 5% are associated with the tumor suppressor syndrome, NF2-related schwannomatosis. However, pathogenic variants in the NF2 gene are by far the most common genetic aberration found in both NF2-related schwannomatosis tumors and sporadic vestibular schwannomas. Indeed, in most schwannomas, loss of both copies of the NF2 gene can be detected. Nonetheless, vestibular schwannomas contain a relatively low overall burden of pathogenic variants in other genes. NF2-related schwannomatosis patients typically present with bilateral vestibular schwannomas at initial diagnosis, but the presence of a unilateral tumor with multiple other NF2-related tumors suggests mosaicism, which is present in ∼50% of de novo cases. A small number of vestibular schwannomas have been associated with LZTR1-related schwannomatosis predisposition, while other schwannoma associated genes do not seem to confer an increased risk to the eighth cranial nerve. This chapter summarizes the major genetic changes found in NF2-related schwannomatosis and sporadic vestibular schwannomas.