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000212544 1001_ $$aTonn, Svenja$$b0
000212544 245__ $$aRisk prediction in early childhood SHH medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than two subgroups.
000212544 260__ $$aOxford$$bOxford Univ. Press$$c2023
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000212544 500__ $$a2023 Aug 3;25(8):1518-1529
000212544 520__ $$aThe 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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000212544 650_7 $$2Other$$aDNA methylation profiling
000212544 650_7 $$2Other$$aMedulloblastoma
000212544 650_7 $$2Other$$aRisk prediction
000212544 650_7 $$2Other$$aSonic hedgehog-activated
000212544 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b1$$udkfz
000212544 7001_ $$aObrecht, Denise$$b2
000212544 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b3$$udkfz
000212544 7001_ $$aSpohn, Michael$$b4
000212544 7001_ $$00000-0002-5669-8546$$avon Hoff, Katja$$b5
000212544 7001_ $$0P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f$$aMilde, Till$$b6$$udkfz
000212544 7001_ $$aPietsch, Torsten$$b7
000212544 7001_ $$aGoschzik, Tobias$$b8
000212544 7001_ $$aBison, Brigitte$$b9
000212544 7001_ $$aJuhnke, Björn-Ole$$b10
000212544 7001_ $$aStruve, Nina$$b11
000212544 7001_ $$0P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807$$aSturm, Dominik$$b12$$udkfz
000212544 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b13$$udkfz
000212544 7001_ $$aBockmayr, Michael$$b14
000212544 7001_ $$aFriedrich, Carsten$$b15
000212544 7001_ $$avon Bueren, André O$$b16
000212544 7001_ $$aGerber, Nicolas U$$b17
000212544 7001_ $$aBenesch, Martin$$b18
000212544 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b19$$udkfz
000212544 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b20$$udkfz
000212544 7001_ $$aWefers, Annika K$$b21
000212544 7001_ $$00000-0002-8731-1121$$aSchüller, Ulrich$$b22
000212544 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b23$$udkfz
000212544 7001_ $$aRutkowski, Stefan$$b24
000212544 7001_ $$00000-0003-3302-2719$$aMynarek, Martin$$b25
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