EVIDENCE FOR SUBARACHNOID SPREAD IN THE DEVELOPMENT OF MULTIPLE MENINGIOMAS

Meningiomas are among the most common human brain tumors. Occasionally patients develop multiple meningiomas. While it has been surmised tha t these are multiple primary meningiomas, it is possible that they rep resent spread of a single primary tumor. Recently, the neurofibromatos is type 2 (NF2) tumor suppressor gene has been shown to carry mutation s in meningiomas. In the present study we have analyzed multiple menin giomas from two patients for point mutations in the NF2 gene by SSCP a nalysis and direct sequencing. We detected point mutations in the meni ngiomas from both patients. The first patient from which six tumors we re available had a three base pair deletion in the splice donor region of exon 7. All tumors showed the identical mutation. The second patie nt with two independent meningiomas had a nonsense mutation in exon 8 which was the same in both tumors. Analysis of constitutional DNA reve aled a wildtype DNA sequence in both cases. There was no family histor y of neurofibromatosis type 2 in either patient. These data provide st rong evidence for a monoclonal origin of multiple meningiomas. Early s ubarachnoid spread is the most likely mechanism for the formation of t hese tumors.