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| Home > Publications database > Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma. > print |
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| 005 | 20240228135106.0 | ||
| 024 | 7 | _ | |a 10.1007/s00401-014-1315-x |2 doi |
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| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Wiestler, Benedikt Paul Otmar |0 P:(DE-He78)2d0c564eca775a62ff86225f7717af12 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma. |
| 260 | _ | _ | |a Berlin |c 2014 |b Springer |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1523525874_11404 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The outcome of patients with anaplastic gliomas varies considerably. Whether a molecular classification of anaplastic gliomas based on large-scale genomic or epigenomic analyses is superior to histopathology for reflecting distinct biological groups, predicting outcomes and guiding therapy decisions has yet to be determined. Epigenome-wide DNA methylation analysis, using a platform which also allows the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas, and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering of DNA methylation patterns revealed two main groups correlated with IDH status: CpG island methylator phenotype (CIMP) positive (77.5 %) or negative (22.5 %). CIMP(pos) (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMP(neg) (IDH wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMP(neg) glioblastomas without forming separate groups based on WHO grade. Notably, there was no molecular evidence for a distinct biological entity representing anaplastic oligoastrocytoma. Tumor classification based on CIMP and 1p/19q status was significantly associated with survival, allowing a better prediction of outcome than the current histopathological classification: patients with CIMP(pos) tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMP(pos) tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMP(neg) anaplastic gliomas (GBM-like) had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped by IDH and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort. |
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| 650 | _ | 7 | |a Nuclear Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Tumor Suppressor Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a DNA Modification Methylases |0 EC 2.1.1.- |2 NLM Chemicals |
| 650 | _ | 7 | |a MGMT protein, human |0 EC 2.1.1.63 |2 NLM Chemicals |
| 650 | _ | 7 | |a Telomerase |0 EC 2.7.7.49 |2 NLM Chemicals |
| 650 | _ | 7 | |a DNA Helicases |0 EC 3.6.4.- |2 NLM Chemicals |
| 650 | _ | 7 | |a ATRX protein, human |0 EC 3.6.4.12 |2 NLM Chemicals |
| 650 | _ | 7 | |a DNA Repair Enzymes |0 EC 6.5.1.- |2 NLM Chemicals |
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| 700 | 1 | _ | |a Pietsch, Torsten |b 17 |
| 700 | 1 | _ | |a Reifenberger, Guido |0 P:(DE-HGF)0 |b 18 |
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| 700 | 1 | _ | |a Weller, Michael |b 24 |
| 700 | 1 | _ | |a Wick, Wolfgang |0 P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee |b 25 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1007/s00401-014-1315-x |g Vol. 128, no. 4, p. 561 - 571 |0 PERI:(DE-600)1458410-4 |n 4 |p 561 - 571 |t Acta neuropathologica |v 128 |y 2014 |x 1432-0533 |
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