000125497 001__ 125497
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000125497 0247_ $$2doi$$a10.1038/nm.4204
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000125497 1001_ $$0P:(DE-HGF)0$$aBender, Sebastian$$b0$$eFirst author
000125497 245__ $$aRecurrent MET fusion genes represent a drug target in pediatric glioblastoma.
000125497 260__ $$aNew York, NY$$bNature America Inc.$$c2016
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000125497 500__ $$aBender S*, Gronych J*, Warnatz HJ*, Hutter B*(*shared first and senior authorships)Pfister SM*, Lichter P*, Jones DT*
000125497 520__ $$aPediatric glioblastoma is one of the most common and most deadly brain tumors in childhood. Using an integrative genetic analysis of 53 pediatric glioblastomas and five in vitro model systems, we identified previously unidentified gene fusions involving the MET oncogene in ∼10% of cases. These MET fusions activated mitogen-activated protein kinase (MAPK) signaling and, in cooperation with lesions compromising cell cycle regulation, induced aggressive glial tumors in vivo. MET inhibitors suppressed MET tumor growth in xenograft models. Finally, we treated a pediatric patient bearing a MET-fusion-expressing glioblastoma with the targeted inhibitor crizotinib. This therapy led to substantial tumor shrinkage and associated relief of symptoms, but new treatment-resistant lesions appeared, indicating that combination therapies are likely necessary to achieve a durable clinical response.
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000125497 650_7 $$2NLM Chemicals$$aAnilides
000125497 650_7 $$2NLM Chemicals$$aDNA, Neoplasm
000125497 650_7 $$2NLM Chemicals$$aGSK 1363089
000125497 650_7 $$2NLM Chemicals$$aMicrotubule-Associated Proteins
000125497 650_7 $$2NLM Chemicals$$aOncogene Proteins, Fusion
000125497 650_7 $$2NLM Chemicals$$aProtein Kinase Inhibitors
000125497 650_7 $$2NLM Chemicals$$aProteins
000125497 650_7 $$2NLM Chemicals$$aPyrazoles
000125497 650_7 $$2NLM Chemicals$$aPyridines
000125497 650_7 $$2NLM Chemicals$$aQuinolines
000125497 650_7 $$2NLM Chemicals$$aRNA, Messenger
000125497 650_7 $$2NLM Chemicals$$aTFG protein, human
000125497 650_7 $$2NLM Chemicals$$acytoplasmic linker protein 115
000125497 650_7 $$053AH36668S$$2NLM Chemicals$$acrizotinib
000125497 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aProto-Oncogene Proteins c-met
000125497 650_7 $$0EC 2.7.11.24$$2NLM Chemicals$$aMitogen-Activated Protein Kinases
000125497 650_7 $$0EC 3.1.3.48$$2NLM Chemicals$$aPTPRZ1 protein, human
000125497 650_7 $$0EC 3.1.3.48$$2NLM Chemicals$$aReceptor-Like Protein Tyrosine Phosphatases, Class 5
000125497 7001_ $$00000-0003-0557-679X$$aGronych, Jan$$b1
000125497 7001_ $$00000-0002-0327-9209$$aWarnatz, Hans-Jörg$$b2
000125497 7001_ $$00000-0002-9034-0329$$aHutter, Barbara$$b3$$eFirst author
000125497 7001_ $$aGröbner, Susanne$$b4
000125497 7001_ $$aRyzhova, Marina$$b5
000125497 7001_ $$0P:(DE-He78)c0538fae462bd98e3cd8d54ed885b0eb$$aPfaff, Elke$$b6
000125497 7001_ $$aHovestadt, Volker$$b7
000125497 7001_ $$aWeinberg, Florian$$b8
000125497 7001_ $$aHalbach, Sebastian$$b9
000125497 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b10
000125497 7001_ $$aNorthcott, Paul A$$b11
000125497 7001_ $$00000-0003-0250-1696$$aSturm, Dominik$$b12
000125497 7001_ $$aBjerke, Lynn$$b13
000125497 7001_ $$00000-0001-9848-7598$$aZichner, Thomas$$b14
000125497 7001_ $$aStütz, Adrian M$$b15
000125497 7001_ $$aSchramm, Kathrin$$b16
000125497 7001_ $$aHuang, Bingding$$b17
000125497 7001_ $$00000-0003-0764-5832$$aBuchhalter, Ivo$$b18
000125497 7001_ $$0P:(DE-He78)ae1b30b052ea4c3ea118a5ca3b46adc3$$aHeinold, Michael$$b19
000125497 7001_ $$aRisch, Thomas$$b20
000125497 7001_ $$aWorst, Barbara C$$b21
000125497 7001_ $$avan Tilburg, Cornelis M$$b22
000125497 7001_ $$aWeber, Ursula D$$b23
000125497 7001_ $$00000-0001-8287-5967$$aZapatka, Marc$$b24
000125497 7001_ $$aRaeder, Benjamin$$b25
000125497 7001_ $$aMilford, David$$b26
000125497 7001_ $$aHeiland, Sabine$$b27
000125497 7001_ $$0P:(DE-He78)5bacb661d5d7c0220d8f996d980ad8de$$avon Kalle, Christof$$b28
000125497 7001_ $$aPreviti, Christopher$$b29
000125497 7001_ $$0P:(DE-HGF)0$$aLawerenz, Christian$$b30
000125497 7001_ $$aKulozik, Andreas E$$b31
000125497 7001_ $$aUnterberg, Andreas$$b32
000125497 7001_ $$0P:(DE-He78)143af26de9d57bf624771616318aaf7c$$aWitt, Olaf$$b33
000125497 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b34
000125497 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b35$$udkfz
000125497 7001_ $$aTruffaux, Nathalène$$b36
000125497 7001_ $$aGrill, Jacques$$b37
000125497 7001_ $$aJabado, Nada$$b38
000125497 7001_ $$aSehested, Astrid M$$b39
000125497 7001_ $$aSumerauer, David$$b40
000125497 7001_ $$aBrahim, Dorra Hmida-Ben$$b41
000125497 7001_ $$aTrabelsi, Saoussen$$b42
000125497 7001_ $$aNg, Ho-Keung$$b43
000125497 7001_ $$aZagzag, David$$b44
000125497 7001_ $$aAllen, Jeffrey C$$b45
000125497 7001_ $$00000-0002-7151-6528$$aKarajannis, Matthias A$$b46
000125497 7001_ $$aGottardo, Nicholas G$$b47
000125497 7001_ $$aJones, Chris$$b48
000125497 7001_ $$00000-0002-2798-3794$$aKorbel, Jan O$$b49
000125497 7001_ $$0P:(DE-He78)d6e2a991c1003a27b302b66a5477e6cd$$aSchmidt, Sabine$$b50
000125497 7001_ $$0P:(DE-He78)1efb774993effe7a66a6ffc1b1cf9ccb$$aWolf, Stephan$$b51
000125497 7001_ $$aReifenberger, Guido$$b52
000125497 7001_ $$aFelsberg, Jörg$$b53
000125497 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b54
000125497 7001_ $$aHerold-Mende, Christel$$b55
000125497 7001_ $$aLehrach, Hans$$b56
000125497 7001_ $$aBrummer, Tilman$$b57
000125497 7001_ $$aKorshunov, Andrey$$b58
000125497 7001_ $$0P:(DE-He78)78b6aa82148e60b4d91e3a37a6d3d9a0$$aEils, Roland$$b59
000125497 7001_ $$00000-0002-9555-9979$$aYaspo, Marie-Laure$$b60
000125497 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b61$$eLast author
000125497 7001_ $$0P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c$$aLichter, Peter$$b62$$eLast author
000125497 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b63$$eLast author
000125497 7001_ $$0P:(DE-HGF)0$$a, , International Cancer Genome Consortium PedBrain Tumor Project.$$b64$$eCollaboration author
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