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Figure J.
Localization of the three putative loci on the long arm of chromosome 22 involved in meningioma
development.
in the disruption of a subsequently isolated MNI gene at the translocation breakpoint (Chapter
VI). The second patient, who developed multiple meningiomas, was the carrier of a
constitutional interstitial deletion of 1,5 kb. This deletion was mapped about 10 kb proximal
to the MNI gene (Chapter VII). In both cases mutations in the NF2 gene (see below) were
not observed (Chapter VIII).
The second locus at band 22q12 is positioned about 1.7 Mb distal to the MNI gene.
This loclis harbours two genes, which both showed alterations in meningiomas. The first
gene is the NF2 gene recently isolated by two independent groups (Trofatter et aI., 1993;
Rouleau et aI., 1993). In both NF2 associated and sporadic meningiomas mutations in the
NF2 gene have been observed (section 3.7 and Chapter VIII). This implies that mutations in
the NF2 gene are important in the development of sporadic meningiomas. As yet it is not
known if a mutation in this gene is a prerequisite for the development of meningiomas. The
second gene is the MEN gene (candidate meningioma gene) located 200 kb centromeric to
the NF2 gene. This gene has been isolated from a region which was homozygously deleted
in one meningioma and codes for a fi-adaptin protein. The deletion did not include the NF2
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