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were derived from patients with more than two meningiomas located at different sites in the
brain. Moreover, one or more of the mentioned subclasses of meningiomas (Chapter III)
might be the result of mutations in different genes.
The search for genes that might playa role in menigioma development have resulted in the
isolation of two genes and the suspected involvement of at least two others that are still
unknown. Therefore, much more research is required to completely understand the
pathogenesis and progression of meningiomas. Concerning the MNI gene, mutation analysis
in meningiomas must be performed to investigate the importance of this gene in meningioma
development in general. This mutation analysis should be extended to other tumor types with
aberrations of chromosome 22 in order to determine the role of MN I in cancer development.
At present it is not clear whether MNI gene mutations are the primary or secondary cause
of tumor development in (some) meningiomas. Interesting in this respect is the observation
that meningioma 32 cells could be cultured for a very long time, whereas other meningioma
cultures stopped dividing after a few weaks or became overgrown by normal cells initially
present in low numbers in the cell cultures. Therefore, alterations of MNI might contribute
to immortalisation. Functional studies such as transfection experiments of mutated or wHdtype
MNl, the generation of (knock-out) transgenic mice and protein studies should provide
insight into the normal function of the MNI gene and its contribution to neoplastic disease.
Recent work by others and our mutation study have clearly indicated that the NF2 gene is
involved in meningioma development. Sequence comparison of the NF2 gene with moesin,
ezrin and radixin suggests that this gene plays a role in mediating interactions between the
cell membrane and the cytoskeleton. These findings should facilitate future studies about the
exact role of this gene in tumorigenesis. The generation of antibodies and transgenic animals
might provide useful tools for this analysis.
Cloning of the as yet unkown genes and the continuation of mutation analysis of all identified
putative meningioma genes might result in a better understanding of the involvement of the
individual genes and might eventually lead to a model for meningioma development.
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