Loss of Heterozygosity for Loci on Chromosome 10 Is Associated with Morphologically Malignant Meningioma Progression

Abstract

Meningioma is a common tumor of the central nervous system which displays morphological heterogeneity. In order to determine whether this phenotypic variability is associated with distinct or overlapping genetic lesions, we compared genotypes at several loci defined by allele length polymorphism in tumor and normal tissues from patients with meningioma. In particular, we concentrated on loci on chromosomes 22 and 10 because these genomic regions have previously been shown to be altered in the former in sporadic and familial meningiomas and in the latter as a late stage event in progression of another common brain tumor, astrocytoma. We examined 38 tumors which were classified as benign, atypical, or malignant by morphological criteria, invasive characteristics, or both. We found that loss of heterozygosity (LOH) for loci on chromosome 22 occurred in 5 of 15 benign, 2 of 2 atypical, and 5 of 10 malignant meningiomas. Similar alterations of chromosome 10 were found in 0 of 20 benign, 1 of 2 atypical, and 4 of 13 malignant meningiomas. Among the malignant tumors, LOH for loci on chromosome 10 occurred in 2 of 4 morphologically malignant tumors and in 2 of 4 morphologically and invasively malignant tumors. In contrast, LOH was not observed for any of the 5 informative tumors classified as malignant by invasive characteristics only. LOH for loci on chromosome 22 accompanied (but was not restricted to) allelic loss of loci on chromosome 10. These data suggest that the progression of meningiomas from arachnoidal cells to the morphologically malignant phenotype may, in part, entail the loss of a tumor suppressor gene(s) on chromosome 22 early in the process and that this may be compounded by alterations of chromosome 10, the LOH of which is associated with morphological signs of malignancy.