000125369 001__ 125369 000125369 005__ 20240228145525.0 000125369 0247_ $$2doi$$a10.1038/nature22973 000125369 0247_ $$2pmid$$apmid:28726821 000125369 0247_ $$2ISSN$$a0028-0836 000125369 0247_ $$2ISSN$$a1476-4687 000125369 0247_ $$2altmetric$$aaltmetric:22201156 000125369 037__ $$aDKFZ-2017-01502 000125369 041__ $$aeng 000125369 082__ $$a070 000125369 1001_ $$0P:(DE-HGF)0$$aNorthcott, Paul A$$b0$$eFirst author 000125369 245__ $$aThe whole-genome landscape of medulloblastoma subtypes. 000125369 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2017 000125369 3367_ $$2DRIVER$$aarticle 000125369 3367_ $$2DataCite$$aOutput Types/Journal article 000125369 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1660899670_27718 000125369 3367_ $$2BibTeX$$aARTICLE 000125369 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000125369 3367_ $$00$$2EndNote$$aJournal Article 000125369 520__ $$aCurrent therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and enhancer hijacking events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma. 000125369 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0 000125369 588__ $$aDataset connected to CrossRef, PubMed, 000125369 7001_ $$0P:(DE-He78)e84b3187ddd3529f884082e30f228c66$$aBuchhalter, Ivo$$b1$$eFirst author 000125369 7001_ $$aMorrissy, A Sorana$$b2 000125369 7001_ $$0P:(DE-He78)744146d3b5a3df1e0ac555e5bf1ee5cc$$aHovestadt, Volker$$b3 000125369 7001_ $$aWeischenfeldt, Joachim$$b4 000125369 7001_ $$aEhrenberger, Tobias$$b5 000125369 7001_ $$0P:(DE-He78)932918ed0e8d8790a81235528019a8e0$$aGröbner, Susanne$$b6 000125369 7001_ $$aSegura-Wang, Maia$$b7 000125369 7001_ $$aZichner, Thomas$$b8 000125369 7001_ $$aRudneva, Vasilisa A$$b9 000125369 7001_ $$aWarnatz, Hans-Jörg$$b10 000125369 7001_ $$aSidiropoulos, Nikos$$b11 000125369 7001_ $$aPhillips, Aaron H$$b12 000125369 7001_ $$aSchumacher, Steven$$b13 000125369 7001_ $$0P:(DE-He78)e053817bc90becc8a8dd8250e677e773$$aKleinheinz, Kortine$$b14 000125369 7001_ $$aWaszak, Sebastian M$$b15 000125369 7001_ $$0P:(DE-He78)df8660bc5aba525f7fb6dba4aac15c1c$$aErkek, Serap$$b16 000125369 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b17 000125369 7001_ $$0P:(DE-He78)fae1bf941c5fd76cf5356ecfa1243cc4$$aWorst, Barbara$$b18 000125369 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b19 000125369 7001_ $$0P:(DE-He78)1beba8f953e7ae7e96e8d3e9a48f10f7$$aZapatka, Marc$$b20 000125369 7001_ $$0P:(DE-He78)bff9e3e3d86865d2b0836bb8f3ce98f3$$aJäger, Natalie$$b21 000125369 7001_ $$0P:(DE-HGF)0$$aChavez, Lukas$$b22 000125369 7001_ $$0P:(DE-He78)135e8c8d1dd1b66b8127c3d1e3a9b6a0$$aHutter, Barbara$$b23 000125369 7001_ 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