FREQUENT NF2 GENE TRANSCRIPT MUTATIONS IN SPORADIC MENINGIOMAS AND VESTIBULAR SCHWANNOMAS

The gene for the hereditary disorder neurofibromatosis type 2 (NF2), w hich predisposes for benign CNS tumors such as vestibular schwannomas and meningiomas, has been assigned to chromosome 22 and recently has b een isolated. Mutations in the NF2 gene were found in both sporadic me ningiomas and vestibular schwannomas. However, so far only 6 of the 16 exons of the gene have been analyzed. In order to extend the analysis of an involvement of the NF2 gene in the sporadic counterparts of the se NF2-related tumors, we have used reverse transcriptase-PCR amplific ation followed by SSCP and DNA sequence analysis to screen for mutatio ns in the coding region of the NF2 gene. Analysis of the NF2 gene tran script in 53 unrelated patients with meningiomas and vestibular schwan nomas revealed mutations in 32% of the sporadic meningiomas (n = 44), in 50% of the sporadic vestibular schwannomas (n = 4), in 100% of the tumors found in NF2 patients (n = 2), and in one of three tumors from multiple-meningioma patients. Of the 18 tumors in which a mutation in the NF2 gene transcript was observed and the copy number of chromosome 22 could be established, 14 also showed loss of (parts of) chromosome 22. This suggests that in sporadic meningiomas and NF2-associated tum ors the NF2 gene functions as a recessive tumor-suppressor gene. The m utations detected resulted mostly in frameshifts, predicting truncatio ns starting within the N-terminal half of the putative protein.