%0 Journal Article
%A Mock, Andreas
%A Geisenberger, Christoph
%A Orlik, Christian
%A Warta, Rolf
%A Schwager, Christian
%A Jungk, Christine
%A Dutruel, Céline
%A Geiselhart, Lea
%A Weichenhan, Dieter
%A Zucknick, Manuela
%A Nied, Ann-Katrin
%A Friauf, Sara
%A Exner, Janina
%A Capper, David
%A Hartmann, Christian
%A Lahrmann, Bernd
%A Grabe, Niels
%A Debus, Jürgen
%A von Deimling, Andreas
%A Popanda, Odilia
%A Plass, Christoph
%A Unterberg, Andreas
%A Abdollahi, Amir
%A Schmezer, Peter
%A Herold-Mende, Christel
%T LOC283731 promoter hypermethylation prognosticates survival after radiochemotherapy in IDH1 wild-type glioblastoma patients.
%J International journal of cancer
%V 139
%N 2
%@ 0020-7136
%C Bognor Regis
%I Wiley-Liss
%M DKFZ-2017-05262
%P 424 - 432
%D 2016
%X MGMT 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.
%K Isocitrate Dehydrogenase (NLM Chemicals)
%K IDH1 protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:26934681
%R 10.1002/ijc.30069
%U https://inrepo02.dkfz.de/record/130182