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Introduction
Meningiomas are considered to be histologically benign neoplasms that account for 13-19%
of all primary brain tumors treated by surgery (Russell and Rubinstein 1989), However, all
meningiomas may display, to a certain extent, atypical or anaplastic features (JaaskeHiinen
et aI., 1985),
Cytogenetically, meningiomas are the most extensively studied human solid tumors
and they display a consistent chromosome aberration (Zang and Singer, 1967; Zang, 1982),
These cytogenetic studies and molecular genetic analyses strongly suggest that loss of (parts
of) chromosome 22 is a primary event in the development of these tumors and also indicate
that several chromosome 22 loci might be involved in the process (Seizinger et aI., 1987;
Rey et aI., 1988; Dumanski et aI., 1990; Lekanne Deprez et aI., 1991a; Rey et aI., 1993;
Lekanne Deprez et aI., 1994). In addition, other less common non random chromosomal
changes occur in some tumors, which might playa role in tumor progression (Katsuyama et
aI., 1986; Al Saadi et aI., 1987; Casalone et aI., 1987; Maltby et aI., 1988; Rey et aI., 1988;
Vagner-Capodano et aI., 1993; Biegel et aI., 1994), One of these changes could also be the
primary cause in a subset of meningiomas without chromosome 22 involvement, as a
meningioma/ependymoma family did not show linkage to DNA markers flanking the NF2
locus on chromosome 22 (Pulst et aI., 1993). More complex chromosome abnormalities
appear to be associated with more atypical features (Vagner-Capodano et aI., (993),
Most meningiomas occur sporadically, although they are also found in patients with
the autosomal dominantly inherited predisposition for Neurofibromatosis type 2 (NF2) or in
multiple meningioma patients or very rarely as sole tumor type clustered in some families
(Butti et ai" 1989; Domenicicci et aI., 1989; Russell and Rubinstein, 1989; McDowell,
1990; Sieb et aI., (992), Positional cloning approaches have resulted in the isolation of the
NF2 gene on chromosome 22q12 and mutations were observed in both the germ-line of NF2
patients and in sporadic tumors (Rouleau et aI., 1993; Trofalter et aI., 1993), Recently,
mutation analyses of the NF2 gene have revealed mutations in about 30% of the sporadic
meningiomas (Lekanne Deprez et aI., 1994; Ruttledge et aI., 1994), This indicates that the
NF2 gene is important in the development of a large number of sporadic meningiomas,
although it is still very well possible that other loci on chromosome 22 and/or other
chromosomes are involved (see above). Studies on the association between chromosomal
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