The molecular biology of vestibular schwannomas: dissecting the pathogenic process at the molecular level.

OBJECTIVE: The goal of this article was to review concisely what is currently known about the tumorigenesis of vestibular schwannomas.

BACKGROUND: Recent advances in molecular biology have led to a better understanding of the cause of vestibular schwannomas. Mutations in the neurofibromatosis type 2 tumor suppressor gene (NF2) have been identified in these tumors. In addition, the interactions of merlin, the protein product of the NF2 gene, and other cellular proteins are beginning to give us a better idea of NF2 function and the pathogenesis of vestibular schwannomas.

METHODS: Review of the relevant basic science studies at our institution as well as the basic science and clinical literature.

RESULTS: The clinical characteristics of vestibular schwannomas and neurofibromatosis type 2 syndromes are reviewed and related to alterations in the NF2 gene. Studies demonstrating our current understanding of tumor developmental pathways are highlighted. In addition, methods of clinical and genetic screening for neurofibromatosis type 2 disease are outlined. Avenues for the development of potential future research and therapies are discussed.

CONCLUSION: Great strides have been made to identify why vestibular schwannomas develop at the molecular level. Continued research is needed to find targeted therapies with which to treat these tumors.