Comparative analysis of theNF2, TP53, PTEN, KRAS, NRAS andHRAS genes in sporadic and radiation-induced human meningiomas

Abstract

Irradiation to the head is associated with a significantly increased incidence of meningiomas. Radiation-induced meningiomas morphologically resemble their sporadically arising counterparts; however, they frequently exhibit a more malignant phenotype. Several genes have been shown to carry mutations in meningiomas, with the NF2 gene being most frequently affected. To examine whether the NF2 gene also plays a role in the development of radiation-induced meningiomas, we compiled a series of meningiomas from 25 patients with a history of previous cranial radiation. This series was compared with 21 atypical WHO grade II meningiomas and 15 anaplastic WHO grade III meningiomas, all from patients without a history of prior irradiation. NF2 mutations occurred significantly more often in sporadic atypical and anaplastic than in radiation-induced meningiomas (p < 0.02). In addition, all meningiomas 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 tumor were detected. PTEN mutations were observed in 1 anaplastic and 1 radiation-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 pathogenesis of radiation-induced compared to sporadic meningiomas.