omic Profiling Reveals Alternative Genetic Pathways of ingioma Malignant Progression Dependent

Download pose: Meningiomas are the most common central nervous system tumors in the population of age d older. WHO defines three grades predictive of the risk of recurrence. Clinical data supporting ogic malignant progression of meningiomas are sparse and underlying molecular mechanisms t clearly depicted. erimental Design: We identified genetic alterations associated with histologic progression of 36 meningioma samples in 18 patients using 500K SNP genotyping arrays and NF2 gene sequencing. ults: The most frequent chromosome alterations observed in progressing meningioma samples are lterations (i.e., present both in lowerand higher-grade samples of a single patient). In our series, ene inactivation was an early and frequent event in progressing meningioma samples (73%). Chrome alterations acquired during progression from grade I to grade II meningioma were not recurrent. ssion to grade III was characterized by recurrent genomic alterations, the most frequent being 2A/CDKN2B locus loss on 9p. clusion: Meningiomas displayed different patterns of genetic alterations during progression acg to their NF2 status: NF2-mutated meningiomas showed higher chromosome instability during ssion than NF2-nonmutated meningiomas, which had very few imbalanced chromosome segprogre ments. This pattern of alterations could thus be used as markers in clinical practice to identify tumors prone to progress among grade I meningiomas. Clin Cancer Res; 16(16); 4155–64. ©2010 AACR.