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| Home > Publications database > LOC283731 promoter hypermethylation prognosticates survival after radiochemotherapy in IDH1 wild-type glioblastoma patients. > print |
| 001 | 130182 | ||
| 005 | 20240228143414.0 | ||
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| 100 | 1 | _ | |a Mock, Andreas |b 0 |
| 245 | _ | _ | |a LOC283731 promoter hypermethylation prognosticates survival after radiochemotherapy in IDH1 wild-type glioblastoma patients. |
| 260 | _ | _ | |a Bognor Regis |c 2016 |b Wiley-Liss |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a 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. |
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| 650 | _ | 7 | |a Isocitrate Dehydrogenase |0 EC 1.1.1.41 |2 NLM Chemicals |
| 650 | _ | 7 | |a IDH1 protein, human |0 EC 1.1.1.42. |2 NLM Chemicals |
| 700 | 1 | _ | |a Geisenberger, Christoph |b 1 |
| 700 | 1 | _ | |a Orlik, Christian |b 2 |
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| 700 | 1 | _ | |a Jungk, Christine |b 5 |
| 700 | 1 | _ | |a Dutruel, Céline |b 6 |
| 700 | 1 | _ | |a Geiselhart, Lea |b 7 |
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| 700 | 1 | _ | |a Hartmann, Christian |b 14 |
| 700 | 1 | _ | |a Lahrmann, Bernd |b 15 |
| 700 | 1 | _ | |a Grabe, Niels |b 16 |
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| 700 | 1 | _ | |a Unterberg, Andreas |b 21 |
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| 700 | 1 | _ | |a Herold-Mende, Christel |b 24 |
| 773 | _ | _ | |a 10.1002/ijc.30069 |g Vol. 139, no. 2, p. 424 - 432 |0 PERI:(DE-600)1474822-8 |n 2 |p 424 - 432 |t International journal of cancer |v 139 |y 2016 |x 0020-7136 |
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