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expression of the MNI gene in one of the tumors. Furthermore, the father of this patient
revealed the same germ-line alterations without signs of meningiomas. Thus so far, the
involvement of the MNI gene in meningioma development in this patient remains an open
question.
The recent cloning of the NF2 gene, which is located about I, 7 Mb distal to the MN 1 gene,
suggests that different genes on chromosome 22 might play a role in meningioma
development. To elucidate the extent in which the NF2 gene is involved in meningioma
development we performed RT-PCR SSCP mutation analysis in 44 sporadic meningiomas
(Chapter VIII). Tn 14 tumors mutations, predominantly resulting in premature termination of
the putative protein, were observed and this often was accompanied by loss of (parts ot)
chromosome 22. These results suggest that inactivating mutations of the NF2 gene are
frequently involved in sporadic meningioma development and that this gene functions as a
recessive tumor suppressor gene. However, in both meningioma 32 and patient 55, with
aberrations in or close to the MNI gene we were not able to identify mutations in the NF2
gene using the RT-PCR SSCP approach.
In addition to the isolated NF2 and MNI genes, other studies suggest even more loci involved
in meningioma development. Molecular genetic analyses in two meningiomas revealed
aberrations distal to the NF2 gene on chromosome 22. Furthermore, recently linkage analysis
in a meningioma/ependymoma family excluded 15 Mb of chromosome 22, including the NF2
gene, as the region harbouring the predisposing mutation. This indicates that another
menigioma loclls exists probably on another chromosome. This hypothesis assllmes that
mutations in different genes can lead to the development of the same tumor type. Such a
situation resembles the development of \Vilms' tumors in which three loci, two on
chromosome IIp and a third one still unknown, have been identified. One obvious
explanation for this observation might be that all these putative genes participate in the same
signal transduction pathway and that abrogation of separate steps in the pathway can lead to
the same type of tumor. Another possibility might be that these different genetic alterations
are responsible for the development of the same tumor type with specific for instance
histologiCal characteristics or that a combination of both takes place. Interesting in this
respect is the fact that both meningiomas showing alterations in or close to the MNJ gene
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