Radiation-induced meningioma: A distinct molecular genetic pattern?

Radiation-induced meningiomas arise after low-dose irradiation treatment of certain medical conditions and are recognized as clinically separate from sporadic meningioma. These tumors are often aggressive or malignant, they a re likely to be multiple, and they have a high recurrence rate following tr eatment compared with sporadic meningiomas. To understand the molecular mec hanism by which radiation-induced meningioma (RIM) arise, we compared genet ic changes in 7 RIM and 8 sporadic meningioma (SM) samples. The presence of mutations in the 17 exons of the neurofibromatosis type 2 (NF2) gene, whic h has been shown to be inactivated in sporadic meningiomas, was analyzed in RIM and SM using single-strand conformation polymorphism (SSCP) and DNA se quencing. In contrast to SM, which showed NF2 mutations in 50% of specimens , no mutations were found in RIM. In addition, Western blot analysis of sch wannomin/merlin protein, the NF2 gene product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor samples analyzed. Loss of heter ozygosity (LOH) of genomic regions, which were reported for SM, was also an alyzed in all cases of RIM using 22 polymorphic DNA markers. Allele losses were found on chromosomes Ip (4/7), 9p (2/7), 19q (2/7), 22q (2/7), and 18q (1/7). From these observations we conclude that unlike sporadic meningioma s, NF2 gene inactivation and chromosome 22q deletions are far less frequent in RIM, and their role in meningioma development following low dose irradi ation is less significant. Other chromosomal lesions, especially loss of Ip , possibly induced by irradiation, may be more important in the development of these tumors.