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 are likely to be multiple, and they have a high recurrence rate following treatment compared with sporadic meningiomas. To understand the molecular mechanism by which radiation-induced meningioma (RIM) arise, we compared genetic 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, which has been shown to be inactivated in sporadic meningiomas, was analyzed in RIM and SM using single-strand conformation polymorphism (SSCP) and DNA sequencing. In contrast to SM, which showed NF2 mutations in 50% of specimens, no mutations were found in RIM. In addition, Western blot analysis of schwannomin/merlin protein, the NF2 gene product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor samples analyzed. Loss of heterozygosity (LOH) of genomic regions, which were reported for SM, was also analyzed in all cases of RIM using 22 polymorphic DNA markers. Allele losses were found on chromosomes 1p (4/7), 9p (2/7), 19q (2/7), 22q (2/7), and 18q (1/7). From these observations we conclude that unlike sporadic meningiomas, NF2 gene inactivation and chromosome 22q deletions are far less frequent in RIM, and their role in meningioma development following low dose irradiation is less significant. Other chromosomal lesions, especially loss of 1p, possibly induced by irradiation, may be more important in the development of these tumors.
Shoshan
Y
Y
Center for Molecular Genetics, Department of Neurosurgery, The Cleveland Clinical Foundation, Ohio 44195, USA.
Chernova
O
O
Juen
S S
SS
Somerville
R P
RP
Israel
Z
Z
Barnett
G H
GH
Cowell
J K
JK
D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D016147:Genes, Tumor Suppressor / Q000528:radiation effects; D005820:Genetic Testing; D006801:Humans; D019656:Loss of Heterozygosity / Q000528:radiation effects; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008577:Meningeal Neoplasms / Q000235:genetics*; D008579:Meningioma / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D025581:Neurofibromin 2; D018807:Polymorphism, Single-Stranded Conformational
D008565:Membrane Proteins; D025581:Neurofibromin 2