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early cell cultures the presence of SV 40 related T antigens was described (Weiss et a1., 1975;
Scherneck et aI., 1979; Krieg et aI., 1981). However, these findings were not confirmed by
others (Merletti et a1., 1975).
4.6 Cytogenetic and molecular genetic studies of meningiomas
As early as 1967, cytogenetic studies showed non-random loss of one G-group chromosome
in meningiomas. This was the first specific chromosomal aberration observed in solid tumors
(Zang and Singer, 1967). The subsequent development of banding techniques and molecular
genetic studies revealed that monosomy of chromosome 22 is the hallmark for these tumors
(Zang, 1982; Seizinger et a1., 1987a; Dumanski et aI., 1990a). In a considerable number of
tumors loss of chromosome 22 is the only cytogenetically visible chromosomal alteration (AI
Saadi et a1., 1987; Maltby et a1., 1988; Vagner-Capodano et aI., 1993). These results
indicate that loss of genetic material from this chromosome is a primary and specific event
in the development of these tumors, which is reminiscent of the involvement of a tumor
suppressor gene(s) as is mentioned in section 2. In addition, other less common non random
chromosomal changes occur. The most frequent ones are loss or rearrangements of
chromosomes 1, 7, 14, 18 and 19 and these are thought to playa role in tumor progression
(Katsuyama et aI., 1986; AI Saadi et aI., 1987; Maltby et aI., 1988; Rey et aI., 1988;
Casalone et aI., 1990). The karyotypic evolution observed in meningiomas appears to be
associated with more anaplastic features (Vagner-Capodano et aI., 1993).
As mentioned earlier the majority of meningiomas are sporadic cases but they are also
found in patients with NF2 or in familial or multiple meningioma patients. Genetic linkage
studies in NF2 families, tumor deletion mapping in both sporadic and hereditary meningioma
cases resulted in the identification of at least three different loci on the long arm of
chromosome 22, which might be involved in the pathogenesis of meningioma. In figure 3 the
three chromosome 22 loci are depicted.
Evidence for the involvement of the most proximal locus in band 22q 11 came from
cytogenetic and molecular genetic findings in two independent patients with meningiomas.
The meningioma from the first patient revealed a reciprocal t(4;22)(pI6;qll), which resulted
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