Analysis of human meningiomas for aberrations of the MADH2, MADH4, APM-1 and DCC tumor suppressor genes on the long arm of chromosome 18

We have previously reported that losses of genomic material from the long a rm of chromosome 18 are frequent in atypical and anaplastic meningiomas but rare in benign meningiomas. In the present study, we have investigated a s eries of 37 meningiomas for mutation and expression of 4 tumor suppressor g enes (MADH2, MADH4, APM-1 and DCC) located at 18q21. Comparative genomic hy bridization or loss of heterozygosity analysis showed losses on chromosome 18 that included sequences from 18q21 in 15 of 37 tumors. Mutation analysis of APM-1 revealed a missense mutation (c. 1819G > A: G607S) in 1 atypical meningioma, None of the tumors showed mutations of MADH2 and MADH4 or loss of detectable transcripts from MADH2, MADH4 APM-land DCC. In contrast to hu man brain tissue, normal leptomeninges and meningiomas showed preferential expression of a DCC splice variant lacking 60 base pairs from exon 17. Take n together, our data do not support a significant role for MADH2, MADH4, AP M-1 and DCC alterations in the pathogenesis of meningiomas. The targeted ge ne that is inactivated in most meningiomas with 18q losses remains to be id entified. (C) 2001 Wiley-Liss, Inc.