LOSS OF HETEROZYGOSITY FOR LOCI ON CHROMOSOME-10 IS ASSOCIATED WITH MORPHOLOGICALLY MALIGNANT MENINGIOMA PROGRESSION

Meningioma is a common tumor of the central nervous system which displ ays morphological heterogeneity. In order to determine whether, this p henotypic variability is associated with distinct or overlapping genet ic lesions, we compared genotypes at several loci defined by allele le ngth polymorphism in tumor and normal tissues from patients with menin gioma. In particular, we concentrated on loci on chromosomes 22 and 10 because these genomic regions have previously been shown to be altere d in the former in sporadic and familial meningiomas and in the latter as a late stage event in progression of another common brain tumor, a strocytoma. We examined 38 tumors which were classified as benign, aty pical, or malignant by morphological criteria, invasive characteristic s, or both. We found that loss of heterozygosity (LOH) for loci on chr omosome 22 occurred in 5 of 15 benign, 2 of 2 atypical, and 5 of 10 ma lignant meningiomas. Similar alterations of chromosome 10 were found i n 0 of 24) 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 fo r any of the 5 informative tumors classified as malignant by invasive characteristics only. LOH for loci on chromosome 22 accompanied (but w as not restricted to) allelic loss of loci on chromosome 10. These dat a suggest that the progression of meningiomas from arachnoidal cells t o the morphologically malignant phenotype may, in part, entail the los s 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 L OH of which is associated with morphological signs of malignancy.