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| 001 | 132739 | ||
| 005 | 20240229105030.0 | ||
| 024 | 7 | _ | |a 10.1158/1078-0432.CCR-17-2243 |2 doi |
| 024 | 7 | _ | |a pmid:29351917 |2 pmid |
| 024 | 7 | _ | |a 1078-0432 |2 ISSN |
| 024 | 7 | _ | |a 1557-3265 |2 ISSN |
| 024 | 7 | _ | |a altmetric:31967185 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2018-00393 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Gómez, Soledad |b 0 |
| 245 | _ | _ | |a A Novel Method for Rapid Molecular Subgrouping of Medulloblastoma. |
| 260 | _ | _ | |a Philadelphia, Pa. [u.a.] |c 2018 |b AACR |
| 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 1524828062_15100 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Purpose: The classification of medulloblastoma into WNT, SHH, group 3, and group 4 subgroups has become of critical importance for patient risk stratification and subgroup-tailored clinical trials. Here, we aimed to develop a simplified, clinically applicable classification approach that can be implemented in the majority of centers treating patients with medulloblastoma.Experimental Design: We analyzed 1,577 samples comprising previously published DNA methylation microarray data (913 medulloblastomas, 457 non-medulloblastoma tumors, 85 normal tissues), and 122 frozen and formalin-fixed paraffin-embedded medulloblastoma samples. Biomarkers were identified applying stringent selection filters and Linear Discriminant Analysis (LDA) method, and validated using DNA methylation microarray data, bisulfite pyrosequencing, and direct-bisulfite sequencing.Results: Using a LDA-based approach, we developed and validated a prediction method (EpiWNT-SHH classifier) based on six epigenetic biomarkers that allowed for rapid classification of medulloblastoma into the clinically relevant subgroups WNT, SHH, and non-WNT/non-SHH with excellent concordance (>99%) with current gold-standard methods, DNA methylation microarray, and gene signature profiling analysis. The EpiWNT-SHH classifier showed high prediction capacity using both frozen and formalin-fixed material, as well as diverse DNA methylation detection methods. Similarly, we developed a classifier specific for group 3 and group 4 tumors, based on five biomarkers (EpiG3-G4) with good discriminatory capacity, allowing for correct assignment of more than 92% of tumors. EpiWNT-SHH and EpiG3-G4 methylation profiles remained stable across tumor primary, metastasis, and relapse samples.Conclusions: The EpiWNT-SHH and EpiG3-G4 classifiers represent a new simplified approach for accurate, rapid, and cost-effective molecular classification of single medulloblastoma DNA samples, using clinically applicable DNA methylation detection methods. Clin Cancer Res; 24(6); 1355-63. ©2018 AACR. |
| 536 | _ | _ | |a 312 - Functional and structural genomics (POF3-312) |0 G:(DE-HGF)POF3-312 |c POF3-312 |f POF III |x 0 |
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| 700 | 1 | _ | |a Garrido-Garcia, Alícia |b 1 |
| 700 | 1 | _ | |a Garcia-Gerique, Laura |b 2 |
| 700 | 1 | _ | |a Lemos, Isadora |b 3 |
| 700 | 1 | _ | |a Suñol, Mariona |b 4 |
| 700 | 1 | _ | |a de Torres, Carmen |b 5 |
| 700 | 1 | _ | |a Kulis, Marta |b 6 |
| 700 | 1 | _ | |a Pérez-Jaume, Sara |b 7 |
| 700 | 1 | _ | |a Carcaboso, Ángel M |b 8 |
| 700 | 1 | _ | |a Luu, Betty |b 9 |
| 700 | 1 | _ | |a Kieran, Mark W |b 10 |
| 700 | 1 | _ | |a Jabado, Nada |b 11 |
| 700 | 1 | _ | |a Kozlenkov, Alexey |b 12 |
| 700 | 1 | _ | |a Dracheva, Stella |b 13 |
| 700 | 1 | _ | |a Ramaswamy, Vijay |b 14 |
| 700 | 1 | _ | |a Hovestadt, Volker |0 P:(DE-He78)744146d3b5a3df1e0ac555e5bf1ee5cc |b 15 |u dkfz |
| 700 | 1 | _ | |a Johann, Pascal |0 P:(DE-He78)3fdc3623477264cb5d0e14f256dbfbb8 |b 16 |u dkfz |
| 700 | 1 | _ | |a Jones, David |0 P:(DE-He78)551bb92841f634070997aa168d818492 |b 17 |u dkfz |
| 700 | 1 | _ | |a Pfister, Stefan |0 P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9 |b 18 |u dkfz |
| 700 | 1 | _ | |a Morales La Madrid, Andrés |b 19 |
| 700 | 1 | _ | |a Cruz, Ofelia |b 20 |
| 700 | 1 | _ | |a Taylor, Michael D |b 21 |
| 700 | 1 | _ | |a Martin-Subero, Jose-Ignacio |b 22 |
| 700 | 1 | _ | |a Mora, Jaume |b 23 |
| 700 | 1 | _ | |a Lavarino, Cinzia |b 24 |
| 773 | _ | _ | |a 10.1158/1078-0432.CCR-17-2243 |g Vol. 24, no. 6, p. 1355 - 1363 |0 PERI:(DE-600)2036787-9 |n 6 |p 1355 - 1363 |t Clinical cancer research |v 24 |y 2018 |x 1557-3265 |
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