JOURNAL ARTICLE
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Somatic neurofibromatosis type 2 gene mutations and growth characteristics in vestibular schwannoma.

BACKGROUND: The growth of hereditary and sporadic vestibular schwannomas shows wide variation, but what determines this is poorly understood.

HYPOTHESIS: In neurofibromatosis type 2 (NF2), there is some correlation between the nature of the germline NF2 gene mutation and phenotype. Somatic mutations in the NF2 gene occur in sporadic tumors, but their relation to tumor behavior is unknown.

METHODS: This study has investigated the molecular pathogenesis of vestibular schwannoma by looking for NF2 gene mutations. The authors have screened 17 exons of the NF2 gene in 91 sporadic vestibular schwannomas, 2 NF2, and 1 vagal schwannoma. These data have been correlated with a clinical growth index and a tumor cell proliferation index, determined using a monoclonal antibody to the proliferating cell nuclear antigen.

RESULTS: Of the 94 tumors studied, 40 somatic gene mutations (38%) have been sequenced in 36 tumors. The mutations included 36 protein truncating mutations, 1 in-frame deletion, 2 splice site mutations, and 1 missense mutation. Regression analysis showed no correlation between the nature of the NF2 gene mutation and either the clinical (R2 = 0.006) or the proliferative index (R2 = 4 x 10(-8).

CONCLUSION: The results of this study show no association between the nature of the intragenic NF2 gene mutation and tumor behavior. It is likely therefore that NF2 gene inactivation is not the only determinant of tumor behavior in vestibular schwannoma.

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