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Summary and Discussion
Meningioma is a common benign central nervOllS system tumor (eNS) arising from
arachnoidal cells surrounding the brain and spinal cord. Cytogenetic studies as early as 1967
and molecular genetic analyses revealed that loss of chromosome 22 is the most frequent
aberration observed in these tumors. In additioll, 50% of the patients with the autosomal
dominant inherited disorder NF2 have meningiomas. Linkage analysis in affected families
has assigned the predisposing gene to chromosome 22. This indicates that both NF2 and
sporadic meningioma presumably are the result of mutations in one Of more genes on
chromosome 22. Consistent and specific chromosome deletions suggest the involvement of
tumor suppressor genes. A tumor suppressor gene plays a role in tumorigenesis when both
alleles of the gene are'inactivated. Loss of such a gene is one of the mechanisms involved
in functional inactivation. Therefore, a ttlillor suppressor gene(s) on chromosome 22 is (are)
probably involved in the development of meningiomas. The goal of the work described in
this thesis was to localize and isolate this (these) gene(s) on chromosome 22.
In order to identify the region(s) on chromosome 22 responsible for meningioma development
we first collected meningiomas for cytogenetic and DNA analysis. At that time only a limited
number of markers from this chromosome were available. Therefore, a chromosome 22
specific phage library was used for the isolation of additional probes. The 25 isolated singlecopy
probes were further characterized by testing whether they recognized restriction
fragment length polymorphisms (RFLPs) on human genomic DNA and they were regionally
localized on chromosome 22 using a panel of somatic cell hybrids. The polymorphic probes
were used to construct a linkage map (Chapter II).
These probes and markers obtained from other laboratories were subsequently used to
investigate our collection of meningiomas. Chapter III describes the results of the combined
cytogenetic and molecular genetic study in OLlr series of meningiomas. Furthermore, the
observed chromosomal changes were compared with other patient and tumor characteristics
and statistically analyzed. In accordance with other reports loss of chromosome 22 was most
frequently observed. We found complete or partial loss of this chromosome in 71 % of the
tumors. Statistical analysis revealed a signiticant association between the number of
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