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000120154 0247_ $$2doi$$a10.1007/s00401-014-1297-8
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000120154 0247_ $$2ISSN$$a1432-0533
000120154 037__ $$aDKFZ-2017-00737
000120154 041__ $$aeng
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000120154 1001_ $$aPöschl, Julia$$b0
000120154 245__ $$aGenomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts.
000120154 260__ $$aBerlin$$bSpringer$$c2014
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000120154 520__ $$aMedulloblastoma is a malignant embryonal brain tumor with highly variable outcome. In order to study the biology of this tumor and to perform preclinical treatment studies, a lot of effort has been put into the generation of appropriate mouse models. The usage of these models, however, has become debatable with the advances in human medulloblastoma subgrouping. This study brings together multiple relevant mouse models and matches genetic alterations and gene expression data of 140 murine tumors with 423 human medulloblastomas in a global way. Using AGDEX analysis and k-means clustering, we show that the Blbp-cre::Ctnnb1(ex3)(Fl/+)Trp53 (Fl/Fl) mouse model fits well to human WNT medulloblastoma, and that, among various Myc- or Mycn-based mouse medulloblastomas, tumors in Glt1-tTA::TRE-MYCN/Luc mice proved to be most specific for human group 3 medulloblastoma. None of the analyzed models displayed a significant match to group 4 tumors. Intriguingly, mice with Ptch1 or Smo mutations selectively modeled SHH medulloblastomas of adulthood, although such mutations occur in all human age groups. We therefore suggest that the infantile or adult gene expression pattern of SHH MBs are not solely determined by specific mutations. This is supported by the observation that human medulloblastomas with PTCH1 mutations displayed more similarities to PTCH1 wild-type tumors of the same age group than to PTCH1-mutated tumors of the other age group. Together, we provide novel insights into previously unrecognized specificity of distinct models and suggest these findings as a solid basis to choose the appropriate model for preclinical studies on medulloblastoma.
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000120154 650_7 $$2NLM Chemicals$$aHedgehog Proteins
000120154 650_7 $$2NLM Chemicals$$aPTCH protein, human
000120154 650_7 $$2NLM Chemicals$$aPatched Receptors
000120154 650_7 $$2NLM Chemicals$$aPatched-1 Receptor
000120154 650_7 $$2NLM Chemicals$$aPtch1 protein, mouse
000120154 650_7 $$2NLM Chemicals$$aReceptors, Cell Surface
000120154 650_7 $$2NLM Chemicals$$aSHH protein, human
000120154 7001_ $$0P:(DE-He78)75cc815aba77c01af41fe20138617e9c$$aStark, Sebastian$$b1$$udkfz
000120154 7001_ $$aNeumann, Philipp$$b2
000120154 7001_ $$0P:(DE-He78)932918ed0e8d8790a81235528019a8e0$$aGröbner, Susanne$$b3$$udkfz
000120154 7001_ $$0P:(DE-He78)0ac2bd1a9fb1823a351ee4434d80808b$$aKawauchi, Daisuke$$b4$$udkfz
000120154 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b5$$udkfz
000120154 7001_ $$0P:(DE-HGF)0$$aNorthcott, Paul A$$b6
000120154 7001_ $$0P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c$$aLichter, Peter$$b7$$udkfz
000120154 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b8$$udkfz
000120154 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b9$$udkfz
000120154 7001_ $$aSchüller, Ulrich$$b10
000120154 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-014-1297-8$$gVol. 128, no. 1, p. 123 - 136$$n1$$p123 - 136$$tActa neuropathologica$$v128$$x1432-0533$$y2014
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