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000127884 1001_ $$0P:(DE-He78)2a8fbc2efe7e5e468472d57f724fe39b$$aZuckermann, Marc$$b0$$eFirst author$$udkfz
000127884 245__ $$aSomatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling.
000127884 260__ $$aLondon$$bNature Publishing Group$$c2015
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000127884 520__ $$aIn vivo functional investigation of oncogenes using somatic gene transfer has been successfully exploited to validate their role in tumorigenesis. For tumour suppressor genes this has proven more challenging due to technical aspects. To provide a flexible and effective method for investigating somatic loss-of-function alterations and their influence on tumorigenesis, we have established CRISPR/Cas9-mediated somatic gene disruption, allowing for in vivo targeting of TSGs. Here we demonstrate the utility of this approach by deleting single (Ptch1) or multiple genes (Trp53, Pten, Nf1) in the mouse brain, resulting in the development of medulloblastoma and glioblastoma, respectively. Using whole-genome sequencing (WGS) we characterized the medulloblastoma-driving Ptch1 deletions in detail and show that no off-targets were detected in these tumours. This method provides a fast and convenient system for validating the emerging wealth of novel candidate tumour suppressor genes and the generation of faithful animal models of human cancer.
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000127884 650_7 $$2NLM Chemicals$$aNeurofibromin 1
000127884 650_7 $$2NLM Chemicals$$aPTCH protein, human
000127884 650_7 $$2NLM Chemicals$$aPatched Receptors
000127884 650_7 $$2NLM Chemicals$$aPatched-1 Receptor
000127884 650_7 $$2NLM Chemicals$$aPtch1 protein, mouse
000127884 650_7 $$2NLM Chemicals$$aReceptors, Cell Surface
000127884 650_7 $$2NLM Chemicals$$aTumor Suppressor Protein p53
000127884 650_7 $$0EC 3.1.3.67$$2NLM Chemicals$$aPTEN Phosphohydrolase
000127884 650_7 $$0EC 3.1.3.67$$2NLM Chemicals$$aPten protein, mouse
000127884 7001_ $$0P:(DE-He78)744146d3b5a3df1e0ac555e5bf1ee5cc$$aHovestadt, Volker$$b1$$udkfz
000127884 7001_ $$0P:(DE-HGF)0$$aKnobbe-Thomsen, Christiane B$$b2
000127884 7001_ $$0P:(DE-He78)1beba8f953e7ae7e96e8d3e9a48f10f7$$aZapatka, Marc$$b3$$udkfz
000127884 7001_ $$0P:(DE-HGF)0$$aNorthcott, Paul A$$b4
000127884 7001_ $$0P:(DE-He78)2f592d9d8339bee07cca3956b7472b61$$aSchramm, Kathrin$$b5$$udkfz
000127884 7001_ $$0P:(DE-HGF)0$$aBelic, Jelena$$b6
000127884 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b7$$udkfz
000127884 7001_ $$aTschida, Barbara$$b8
000127884 7001_ $$aMoriarity, Branden$$b9
000127884 7001_ $$aLargaespada, David$$b10
000127884 7001_ $$aRoussel, Martine F$$b11
000127884 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b12$$udkfz
000127884 7001_ $$0P:(DE-HGF)0$$aReifenberger, Guido$$b13
000127884 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b14$$udkfz
000127884 7001_ $$0P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c$$aLichter, Peter$$b15$$udkfz
000127884 7001_ $$0P:(DE-He78)0ac2bd1a9fb1823a351ee4434d80808b$$aKawauchi, Daisuke$$b16$$udkfz
000127884 7001_ $$0P:(DE-He78)bb186a8b38fef24ebd6f11918ade985d$$aGronych, Jan$$b17$$eLast author$$udkfz
000127884 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/ncomms8391$$gVol. 6, p. 7391 -$$p7391 $$tNature Communications$$v6$$x2041-1723$$y2015
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