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| 001 | 212544 | ||
| 005 | 20240229154914.0 | ||
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| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Tonn, Svenja |b 0 |
| 245 | _ | _ | |a Risk prediction in early childhood SHH medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than two subgroups. |
| 260 | _ | _ | |a Oxford |c 2023 |b Oxford Univ. Press |
| 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 1691151103_20939 |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 |
| 500 | _ | _ | |a 2023 Aug 3;25(8):1518-1529 |
| 520 | _ | _ | |a The prognostic impact of clinical risk factors and DNA methylation patterns in sonic hedgehog (SHH)-activated early childhood desmoplastic/nodular medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were evaluated to better identify patients at risk for relapse.Hundred-forty-four patients with DMB (n=99) or MBEN (n=45) aged <5 years and treated with radiation-sparing approaches, including intraventricular methotrexate in 132 patients, were evaluated.Patients with DMB had less favorable 5-year progression-free survival than MBEN (5y-PFS, 71% [DMB] vs 93% [MBEN]). Patients' age >3 years was associated with more unfavorable 5y-PFS (47% [>3 years] vs 85% [<1 year] vs 84% [1-3 years]). DNA methylation profiles available (n=78) were reclassified according to the 2021 WHO classification into SHH-1 (n=39), SHH-2 (n=38), and SHH-3 (n=1). Hierarchical clustering delineated two subgroups among SHH-2: SHH-2a (n=19) and SHH-2b (n=19). Patients with SHH-2b medulloblastoma were older, predominantly displayed DMB histology, and were more often located in the cerebellar hemispheres. Chromosome 9q losses were more frequent in SHH-2b, while few chromosomal alterations were observed in SHH-2a. SHH-2b medulloblastoma carried a significantly increased relapse risk (5y-PFS: 58% [SHH-2b] vs 83% [SHH-1] vs 95% [SHH-2a]). Subclassification of SHH-2 with key clinical and cytogenetic characteristics was confirmed using two independent cohorts (total n=188). Gene mutation analysis revealed a correlation of SHH-2a with SMO mutations.These data suggest further heterogeneity within early childhood SHH-DMB/MBEN: SHH-2 splits into a very low-risk group SHH-2a enriched for MBEN histology and SMO mutations, and SHH-2b comprising older DMB patients with higher risk of relapse. |
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| 650 | _ | 7 | |a DNA methylation profiling |2 Other |
| 650 | _ | 7 | |a Medulloblastoma |2 Other |
| 650 | _ | 7 | |a Risk prediction |2 Other |
| 650 | _ | 7 | |a Sonic hedgehog-activated |2 Other |
| 700 | 1 | _ | |a Korshunov, Andrey |0 P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93 |b 1 |u dkfz |
| 700 | 1 | _ | |a Obrecht, Denise |b 2 |
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| 700 | 1 | _ | |a Spohn, Michael |b 4 |
| 700 | 1 | _ | |a von Hoff, Katja |0 0000-0002-5669-8546 |b 5 |
| 700 | 1 | _ | |a Milde, Till |0 P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f |b 6 |u dkfz |
| 700 | 1 | _ | |a Pietsch, Torsten |b 7 |
| 700 | 1 | _ | |a Goschzik, Tobias |b 8 |
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| 700 | 1 | _ | |a Rutkowski, Stefan |b 24 |
| 700 | 1 | _ | |a Mynarek, Martin |0 0000-0003-3302-2719 |b 25 |
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