P05.51 Prognostic impact of genetic alterations and methylation class in meningioma. (19th September 2018)

• Record Type: Journal Article
• Authors: Berghoff, A S; Ricken, G; Rajky, U; Marosi, C; Hainfellner, J A; von Deimling, A; Sahm, F; Preusser, M
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 3
• Page Start: iii314
• Page End: iii315
• Publication Date: 2018-09-19
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy139.377
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: Meningioma is a heterogenous disease in terms of prognosis and precise molecular characterization may support clinical decision-making. Several recurring gene mutations as well as prognostic relevant subgroups using DNA-methylation based information 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 was analyzed using 850k EPIC (Illumina, San Diego, CA, USA) and methylation class (MC) were scored as previously published. 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: Target mutations were evident in 96/127 (75.5%) specimens with mutations in NF2 (42/127; 33.1%), TRAF7 (40/127; 31.5%), KLF4 (27/127; 21.3%) and ARID (25/127; 19.7%) being the most frequently 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 TERT mutation HR 24.9; 95% CI 3.9–159.8; p=0.001; cox regression model) remained statically significant. Conclusions: Molecular profiling including mutational analysis and DNA methylation classification may facilitate more precise prognostic assessment and identification of potential targets for targeted therapy in meningioma patients.