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000130182 1001_ $$aMock, Andreas$$b0
000130182 245__ $$aLOC283731 promoter hypermethylation prognosticates survival after radiochemotherapy in IDH1 wild-type glioblastoma patients.
000130182 260__ $$aBognor Regis$$bWiley-Liss$$c2016
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000130182 520__ $$aMGMT promoter methylation status is currently the only established molecular prognosticator in IDH wild-type glioblastoma multiforme (GBM). Therefore, we aimed to discover novel therapy-associated epigenetic biomarkers. After enrichment for hypermethylated fractions using methyl-CpG-immunoprecipitation (MCIp), we performed global DNA methylation profiling for 14 long-term (LTS; >36 months) and 15 short-term (STS; 6-10 months) surviving GBM patients. Even after exclusion of the G-CIMP phenotype, we observed marked differences between the LTS and STS methylome. A total of 1,247 probes in 706 genes were hypermethylated in LTS and 463 probes in 305 genes were found to be hypermethylated in STS patients (p values < 0.05, log2 fold change ± 0.5). We identified 13 differentially methylated regions (DMRs) with a minimum of four differentially methylated probes per gene. Indeed, we were able to validate a subset of these DMRs through a second, independent method (MassARRAY) in our LTS/STS training set (ADCY1, GPC3, LOC283731/ISLR2). These DMRs were further assessed for their prognostic capability in an independent validation cohort (n = 62) of non-G-CIMP GBMs from the TCGA. Hypermethylation of multiple CpGs mapping to the promoter region of LOC283731 correlated with improved patient outcome (p = 0.03). The prognostic performance of LOC283731 promoter hypermethylation was confirmed in a third independent study cohort (n = 89), and was independent of gender, performance (KPS) and MGMT status (p = 0.0485, HR = 0.63). Intriguingly, the prediction was most pronounced in younger GBM patients (<60 years). In conclusion, we provide compelling evidence that promoter methylation status of this novel gene is a prognostic biomarker in IDH1 wild-type/non-G-CIMP GBMs.
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000130182 650_7 $$0EC 1.1.1.41$$2NLM Chemicals$$aIsocitrate Dehydrogenase
000130182 650_7 $$0EC 1.1.1.42.$$2NLM Chemicals$$aIDH1 protein, human
000130182 7001_ $$aGeisenberger, Christoph$$b1
000130182 7001_ $$aOrlik, Christian$$b2
000130182 7001_ $$aWarta, Rolf$$b3
000130182 7001_ $$0P:(DE-He78)660cb858f5b7062b4ef81f3273372139$$aSchwager, Christian$$b4$$udkfz
000130182 7001_ $$aJungk, Christine$$b5
000130182 7001_ $$aDutruel, Céline$$b6
000130182 7001_ $$aGeiselhart, Lea$$b7
000130182 7001_ $$0P:(DE-He78)ff4024f7bc236e7897d9c18ee19c451f$$aWeichenhan, Dieter$$b8$$udkfz
000130182 7001_ $$0P:(DE-HGF)0$$aZucknick, Manuela$$b9
000130182 7001_ $$aNied, Ann-Katrin$$b10
000130182 7001_ $$aFriauf, Sara$$b11
000130182 7001_ $$aExner, Janina$$b12
000130182 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b13$$udkfz
000130182 7001_ $$aHartmann, Christian$$b14
000130182 7001_ $$aLahrmann, Bernd$$b15
000130182 7001_ $$aGrabe, Niels$$b16
000130182 7001_ $$0P:(DE-He78)8714da4e45acfa36ce87c291443a9218$$aDebus, Jürgen$$b17$$udkfz
000130182 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b18$$udkfz
000130182 7001_ $$0P:(DE-He78)37610ef78c733753f0836ce0e41b9fda$$aPopanda, Odilia$$b19$$udkfz
000130182 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b20$$udkfz
000130182 7001_ $$aUnterberg, Andreas$$b21
000130182 7001_ $$0P:(DE-He78)360c5bc2b71a849e35aca747c041dda7$$aAbdollahi, Amir$$b22$$udkfz
000130182 7001_ $$0P:(DE-He78)141ce740f5d881812d2675147b72ecaf$$aSchmezer, Peter$$b23$$udkfz
000130182 7001_ $$aHerold-Mende, Christel$$b24
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