Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

LOC283731 promoter hypermethylation prognosticates survival after radiochemotherapy in IDH1 wild-type glioblastoma patients

ABSTRACT: 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; 6â??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 Â± 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. Global DNA methylation profiling in 14 long-term and 15 short-term surviving glioblastoma patients. DNA of 7 normal brain samples were pooled to create a control DNA for two-color analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Christel Herold-Mende

PROVIDER: E-GEOD-74561 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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LOC283731 promoter hypermethylation prognosticates survival after radiochemotherapy in IDH1 wild-type glioblastoma patients.

Mock Andreas A Geisenberger Christoph C Orlik Christian C Warta Rolf R Schwager Christian C Jungk Christine C Dutruel Céline C Geiselhart Lea L Weichenhan Dieter D Zucknick Manuela M Nied Ann-Katrin AK Friauf Sara S Exner Janina J Capper David D Hartmann Christian C Lahrmann Bernd B Grabe Niels N Debus Jürgen J von Deimling Andreas A Popanda Odilia O Plass Christoph C Unterberg Andreas A Abdollahi Amir A Schmezer Peter P Herold-Mende Christel C

International journal of cancer 20160318 2

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, ...[more]

PMID: 26934681

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Dataset Information

LOC283731 promoter hypermethylation prognosticates survival after radiochemotherapy in IDH1 wild-type glioblastoma patients

Publications

LOC283731 promoter hypermethylation prognosticates survival after radiochemotherapy in IDH1 wild-type glioblastoma patients.

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