Comparative analysis of the NF2, TP53, PTEN, KRAS, NRAS and HRAS genes in sporadic and radiation-induced human meningiomas

Irradiation to the head is associated with a significantly hr creased incid ence of meningiomas. Radiation-induced me. ningiomas morphologically resemb le their sporadically arising counterparts; however, they frequently exhibi t a more malignant phenotype. Several genes have been shown to carry mutati ons in meningiomas, with the NF2 gene being most frequently affected. To ex amine whether the NF2 gene also plays a role in the development of radiatio n-induced meningiomas, we compiled a series of meningiomas from 25 patients with a history of previous cranial radiation. This series was compared wit h 21 atypical WHO grade If meningiomas and 15 anaplastic WHO grade III meni ngiomas, all from patients without a history of prior irradiation. NF2 muta tions occurred significantly more often in sporadic atypical and anaplastic than in radiation-induced meningiomas (p<0.02). In addition, all meningiom as were examined for mutations in the PTEN, TP53, HRAS, KRAS and NRAS genes . Two mutations in the TP53 gene in a sporadic and a radiation-induced tumo r were detected. PTEN mutations were observed in I anaplastic and I radiati on-induced meningioma. No structural alterations were seen in the RAS genes . Our data suggest that, while there is a certain overlap in the mutational spectrum, NF2 mutations may not play such a prominent role in the pathogen esis of radiation-induced compared to sporadic meningiomas. (C) 2001 Wiley- Liss, Inc.