1P AND 3P DELETIONS IN MENINGIOMAS WITHOUT DETECTABLE ABERRATIONS OR CHROMOSOME-22 IDENTIFIED BY COMPARATIVE GENOMIC HYBRIDIZATION

Meningioma is a common tumor of the meninges covering the central nerv ous system. Although generally a benign tumor, meningioma often recurs and is malignant in 5-10% of all cases. Loss of chromosome 22 loci, a nd specifically inactivation of the NF2 tumor suppressor gene, is cons idered one of several critical steps in the tumorigenesis of meningiom a. However, cytogenetic and molecular investigations have failed to de tect either aberrations of chromosome 22 or mutations in the NF2 gene in approximately 40% of all tumors, thus making it apparent that an al ternative mechanism(s) is responsible for the development of a large f raction of meningiomas. This subset of meningiomas is not distinct wit h regard to clinical and histopathological features from tumors showin g deletions on chromosome 22. It is, therefore, important to attempt t he elucidation of molecular pathway(s) that may operate in the tumorig enesis of these tumors. We used comparative genomic hybridization (CGH ) to identify regions of the genome other-than chromosome 22, contribu ting to the development of meningioma. We analyzed 25 tumors that had undergone detailed LOH analysis on chromosome 22 and were shown to con tain no detectable deletions. Two benign, malignancy grade I, meningio mas showed concurrent deletion of 1p and 3p. These results suggest tha t loss of both 1p and 3p may contribute to meningioma tumorigenesis. T his may represent genetic changes that are alternative to deletions on chromosome 22. (C) 1997 Wiley-Liss, Inc.