Allelic losses in neurofibromatosis 2-associated meningiomas

More than 50% of patients with neurofibromatosis 2 (NF2) develop meningioma s. Recently, a higher proliferative activity, more mitotic figures, and gre ater nuclear pleomorphism have been described for NF2-associated meningioma s compared with sporadic ones. To analyze whether such histological differe nces could reflect underlying genetic differences, we examined 30 meningiom as from 22 NF2 patients for allelic losses on those chromosome arms that ar e frequently affected by deletions in sporadic meningiomas. In addition, we assessed the proliferative activity of the tumors and studied NF2 germline mutations. Twenty-three meningiomas corresponded to WHO grade I (10 fibrou s, 6 psammomatous. 4 transitional, 3 meningothelial) and 7 to WHO grade II. The average MIB-1 index was 1.60 +/- 0.85 (WHO grade I: 1.41 +/- 0.80. WHO grade II: 2.13 +/- 0.82). When compared with several published studies of sporadic meningiomas, the MIB-1 index in NF2-associated meningiomas was not higher. Loss of heterozygosity (LOH) flanking or within the NF2 locus at 2 2q12 was detected in 100% of the tumors. LOH on 1p was the second most freq uent abnormality (40%). followed by losses on 10q (27%), 6q and 14q (24%). 18q (23%), and 9p (17%). LOH on 19q and 17p, which is nor commonly seen in sporadic meningiomas. was also only rarely detected in NF2-associated menin giomas. NF2 gene mutations were detected in 8 of 15 patients analyzed and w ere located in exons 2, 5, 6, 7, and 8. We conclude that sporadic and NF2-a ssociated meningiomas share a common spectrum and frequency of allelic dele tions as well as, in contrast to previous observations. a similar prolifera tive activity.