We conclude that the involvement of the NF2 gene in human tumorigenesis may be restricted to schwannomas and meningiomas, where it is frequently inactivated by a two-hit process.
Recently, somatic mutations of the NF2 gene have been identified in sporadic meningiomas, thus supporting the hypothesis that the NF2 gene is also important in meningioma pathogenesis.
These results provide strong evidence that the suppressor gene on chromosome 22, frequently inactivated in meningioma, is the NF2 gene, and suggest that another gene is involved in the development of 40% of meningiomas.
In order to characterize better the role of the NF2 gene in the genesis of meningiomas we have examined the entire coding sequence of the gene in 125 meningiomas by single-strand conformational polymorphism analysis; furthermore, LOH analysis for markers of 22q has been carried out.
Mutations in the neurofibromatosis 2 (NF2) gene are the predominant cause in the development of sporadic schwannomas and are also involved in the pathogenesis of meningiomas and ependymomas.
How the absence of the NF2 protein may lead to the development of Schwannomas and meningiomas, which are the major manifestations of NF2 in patients, is not clear at present.
The levels of schwannomin/merlin were severely reduced in eight tumors (57%) when compared with the expression levels in the human brain, LTAg2B cells, and the remaining six meningiomas.
Merlin is thought to play a crucial role as a tumor suppressor not only in hereditary NF2-related tumors, but also in sporadic tumors such as schwannomas, meningiomas and gliomas.