Neuro-Oncology, 2018, Vol. 20(suppl6), pp.vi155-vi155
Abstract BACKGROUND Meningioma is a heterogenous disease and precise molecular characterization may support clinical decision-making. Several recurring gene mutations as well as prognostic relevant DNA-methylation classes were recently identified in meningioma. We aimed to validate the recent findings in an independent cohort. METHODS Formalin fixed and paraffin emended samples of 127 meningioma patients (Grade I 40.9%; Grade II: 37.8%; Grade III: 21.3%) were retrieved from the Neuro-Biobank, Institute of Neurology, Medical University of Vienna. Methylation classes (MC) were analyzed using 850k EPIC (Illumina, San Diego, CA, USA) according to the Heidelberg Meningioma Classifier. Panel sequencing for genes reported to impact meningioma, namely NF2, TRAF7, KLF4, ARID, SMO, AKT, TERT, PIK3CA and SUFU was performed as previously outlined. The TRAKLS mutation type was characterized by presence of TRAF7, AKT1, KLF4 or/and SMO mutation. Survival data including progression free survival was retrieved from chart review. RESULTS Meningioma relevant mutations were evident in 96/127 (75.5%) specimens. NF2 (42/127; 33.1%), TRAF7 (40/127; 31.5%), KLF4 (27/127; 21.3%) and ARID (25/127; 19.7%) mutation were the most frequently observed ones. Two or more mutations were observed in 51/127 (40.2%) specimens. MC correlated with presence of target mutations as well as clinical characteristics (p〈0.05; Chi Square test). TRAF7, KLF4 and TERT mutations as well as TRAKLS mutation type associated with progression free survival in univariate analysis (〈0.05; log rank test), however in multivariable analysis only MC (HR 1.9; 95% CI 1.3–2.8; p=0.001; cox regression model) and presence of TERT mutation HR 24.9; 95% CI 3.9–159.8; p=0.001; cox regression model) remained statically significant. CONCLUSIONS Molecular profiling including methylation class and genetic aberrations and may facilitate more precise prognostic assessment and identification of potential targets for targeted therapy in meningioma patients.