CLONALITY OF MULTIPLE MENINGIOMAS

A significant number of patients with meningiomas develop multiple tum ors without anatomical bridges. To understand the mechanism by which m ultiple meningiomas arise, the authors analyzed DNA from 39 multiple m eningiomas in 12 patients to locate alterations in the neurofibromatos is type 2 (NF2) gene. This gene has been shown to be inactivated in me ningiomas. No patient in our series had a family history of meningioma s or NF2. All tumors were investigated by single strand conformation p olymorphism analysis of the entire coding region of the NF2 gene and b y 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 o rigin. All four patients with more than two lesions had clonal meningi omas and four patients with two meningiomas each carried different mut ations in their tumors. Analysis of constitutional DNA revealed a wild -type NF2 sequence in all 12 patients, thus excluding a forme fruste o f NF2 in these cases. Our data demonstrate that the majority of multip le meningiomas with NF2 gene mutations are of somatic and clonal origi n. Spread of tumor cells via the cerebrospinal fluid is the most likel y mechanism to account for the development of these multiple meningiom as.