Clonality of multiple meningiomas

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✓ A significant number of patients with meningiomas develop multiple tumors without anatomical bridges. To understand the mechanism by which multiple meningiomas arise, the authors analyzed DNA from 39 multiple meningiomas in 12 patients to locate alterations in the neurofibromatosis type 2 (NF2) gene. This gene has been shown to be inactivated in meningiomas. No patient in our series had a family history of meningiomas or NF2. All tumors were investigated by single-strand conformation polymorphism analysis of the entire coding region of the NF2 gene and by direct DNA sequencing of altered fragments. The DNA from meningiomas in 10 patients carried NF2 gene mutations. In six of the 10 patients with NF2 mutations, all tumors in the respective individual exhibited the identical DNA alteration in the NF2 gene, thus indicating clonal origin. All four patients with more than two lesions had clonal meningiomas and four patients with two meningiomas each carried different mutations in their tumors. Analysis of constitutional DNA revealed a wild-type NF2 sequence in all 12 patients, thus excluding a forme fruste of NF2 in these cases. Our data demonstrate that the majority of multiple meningiomas with NF2 gene mutations are of somatic and clonal origin. Spread of tumor cells via the cerebrospinal fluid is the most likely mechanism to account for the development of these multiple meningiomas.

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Address reprint requests to: Andreas von Deimling, M.D., Institut für Neuropathologie, Universitätskliniken Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany.

© AANS, except where prohibited by US copyright law.

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    Representative magnetic resonance images and molecular genetic data obtained in two patients with multiple meningiomas. Upper: Data obtained in Case 2 displaying multiple meningiomas confined to the left hemisphere. Six of the lesions examined revealed the identical 3-bp deletion (GTG) in the splice donor region of exon 7 of the NF2 gene. Lower: Data obtained in Case 8 showing two lesions that exhibit different NF2 gene mutations. The meningioma at the left cerebellopontine angle has a 1-bp exchange from wild-type G to mutant T in exon 7 of the NF2 gene; the meningioma of the right occipital region carries a 3-bp pair deletion (CTT) in exon 3.

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