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000120628 1001_ $$aSandén, Emma$$b0
000120628 245__ $$aEstablishment and characterization of an orthotopic patient-derived Group 3 medulloblastoma model for preclinical drug evaluation.
000120628 260__ $$aLondon$$bNature Publishing Group$$c2017
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000120628 520__ $$aMedulloblastomas comprise a heterogeneous group of tumours and can be subdivided into four molecular subgroups (WNT, SHH, Group 3 and Group 4) with distinct prognosis, biological behaviour and implications for targeted therapies. Few experimental models exist of the aggressive and poorly characterized Group 3 tumours. In order to establish a reproducible transplantable Group 3 medulloblastoma model for preclinical therapeutic studies, we acquired a patient-derived tumour sphere culture and inoculated low-passage spheres into the cerebellums of NOD-scid mice. Mice developed symptoms of brain tumours with a latency of 17-18 weeks. Neurosphere cultures were re-established and serially transplanted for 3 generations, with a negative correlation between tumour latency and numbers of injected cells. Xenografts replicated the phenotype of the primary tumour, including high degree of clustering in DNA methylation analysis, high proliferation, expression of tumour markers, MYC amplification and elevated MYC expression, and sensitivity to the MYC inhibitor JQ1. Xenografts maintained maintained expression of tumour-derived VEGFA and stromal-derived COX-2. VEGFA, COX-2 and c-Myc are highly expressed in Group 3 compared to other medulloblastoma subgroups, suggesting that these molecules are relevant therapeutic targets in Group 3 medulloblastoma.
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000120628 7001_ $$aDyberg, Cecilia$$b1
000120628 7001_ $$aKrona, Cecilia$$b2
000120628 7001_ $$aGallo-Oller, Gabriel$$b3
000120628 7001_ $$aOlsen, Thale Kristin$$b4
000120628 7001_ $$aEnríquez Pérez, Julio$$b5
000120628 7001_ $$aWickström, Malin$$b6
000120628 7001_ $$aEstekizadeh, Atosa$$b7
000120628 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b8$$udkfz
000120628 7001_ $$aVisse, Edward$$b9
000120628 7001_ $$aEkström, Tomas J$$b10
000120628 7001_ $$aSiesjö, Peter$$b11
000120628 7001_ $$aJohnsen, John Inge$$b12
000120628 7001_ $$aDarabi, Anna$$b13
000120628 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/srep46366$$gVol. 7, p. 46366 -$$p46366 -$$tScientific reports$$v7$$x2045-2322$$y2017
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