Molecular alterations in the neurofibromatosis Type 2 gene and its proteinrarely occurring in meningothelial meningiomas

Object. The neurofibromatosis Type 2 (NF2) gene is the only tumor suppresso r gene that has been clearly implicated in the development of benign mening iomas. Interestingly, previous data obtained by the authors indicate that r educed NF2 protein expression seldom occurs in meningothelial meningiomas, the most common histological type of meningioma. The goal of the current st udy was to explore further the hypothesis of NF2 gene-independent tumorigen esis of meningothelial meningiomas. Methods. The authors performed a mutational analysis of all 17 exons of the NF2 gene by using single-stranded conformational polymorphism (SSCP). In a ddition, expression levels of the NF2 protein and mu -calpain, a protease s uggested to inactivate the NF2 protein, were determined by immunoblotting a nalysis of 27 meningiomas (20 meningothelial and seven nonmeningothelial). Mutations of the NF2 gene were found in only one (5%) of 20 meningothelial meningiomas and three (43%) of seven nonmeningothelial tumors (Fisher's exa ct test, p = 0.042). The levels of NF2 protein were severely reduced in six (28.5%) of 21 meningothelial meningiomas, in contrast to six (86%) of seve n nonmeningothelial meningiomas (Fisher's exact test, p = 0.023). Activatio n of mu -calpain did not correlate with the status of NF2 protein expressio n in the meningiomas analyzed, demonstrating that mu -calpain activation do es not account for the loss of NF2 protein in meningiomas with apparently n ormal NF2 genes. Conclusions. These results clearly demonstrate that NF2 gene mutations and decreased NF2 protein expression rarely occur in meningothelial meningiomas compared with other histological types of meningiomas. The clinical behavi or of meningothelial meningiomas, however, is similar to that of other beni gn meningiomas. It is likely, therefore, that the tumorigenesis of meningot helial meningiomas is the result of deleterious alterations of genes that h ave final phenotypical effects similar to inactivation of the NF2 gene.