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000285654 1001_ $$00000-0002-1373-8130$$aSchoof, Melanie$$b0
000285654 245__ $$aMouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures.
000285654 260__ $$a[London]$$bNature Publishing Group UK$$c2023
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000285654 520__ $$aPediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and biological as well as clinical characteristics have not been addressed specifically. To gain insights into tumorigenesis and molecular profiles of these tumors, and to ultimately suggest alternative treatment options, we generated a genetically engineered mouse model by breeding hGFAP-cre::Trp53Fl/Fl::lsl-MYCN mice. All mice developed aggressive forebrain tumors early in their lifetime that mimic human HGG-MYCN regarding histology, DNA methylation, and gene expression. Single-cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. High-throughput drug screening using both mouse and human tumor cells finally indicated high efficacy of Doxorubicin, Irinotecan, and Etoposide as possible therapy options that children with HGG-MYCN might benefit from.
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000285654 650_7 $$2NLM Chemicals$$aN-Myc Proto-Oncogene Protein
000285654 650_7 $$2NLM Chemicals$$aMYCN protein, human
000285654 650_2 $$2MeSH$$aHumans
000285654 650_2 $$2MeSH$$aChild
000285654 650_2 $$2MeSH$$aMice
000285654 650_2 $$2MeSH$$aAnimals
000285654 650_2 $$2MeSH$$aN-Myc Proto-Oncogene Protein: genetics
000285654 650_2 $$2MeSH$$aN-Myc Proto-Oncogene Protein: metabolism
000285654 650_2 $$2MeSH$$aNeuroblastoma: metabolism
000285654 650_2 $$2MeSH$$aDisease Models, Animal
000285654 650_2 $$2MeSH$$aGlioma: genetics
000285654 650_2 $$2MeSH$$aMutation
000285654 650_2 $$2MeSH$$aGene Amplification
000285654 7001_ $$00000-0002-5162-5233$$aGodbole, Shweta$$b1
000285654 7001_ $$00000-0002-2488-0706$$aAlbert, Thomas K$$b2
000285654 7001_ $$00000-0002-9769-7080$$aDottermusch, Matthias$$b3
000285654 7001_ $$aWalter, Carolin$$b4
000285654 7001_ $$aBallast, Annika$$b5
000285654 7001_ $$0P:(DE-He78)a05fe89e8d9ccc1fbd56df77464c7856$$aQin, Nan$$b6
000285654 7001_ $$0P:(DE-HGF)0$$aOlivera, Marlena Baca$$b7
000285654 7001_ $$00000-0002-7345-2089$$aGöbel, Carolin$$b8
000285654 7001_ $$00000-0002-9861-2325$$aNeyazi, Sina$$b9
000285654 7001_ $$00000-0003-4664-3848$$aHoldhof, Dörthe$$b10
000285654 7001_ $$aKresbach, Catena$$b11
000285654 7001_ $$00009-0005-7283-9061$$aPeter, Levke-Sophie$$b12
000285654 7001_ $$aEpplen, Gefion Dorothea$$b13
000285654 7001_ $$aThaden, Vanessa$$b14
000285654 7001_ $$aSpohn, Michael$$b15
000285654 7001_ $$0P:(DE-He78)261d2b84aded878003e6e35d18113831$$aBlattner-Johnson, Mirjam$$b16$$udkfz
000285654 7001_ $$00000-0002-5897-3310$$aModemann, Franziska$$b17
000285654 7001_ $$00000-0003-3302-2719$$aMynarek, Martin$$b18
000285654 7001_ $$aRutkowski, Stefan$$b19
000285654 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b20$$udkfz
000285654 7001_ $$00000-0002-7206-3719$$aVarghese, Julian$$b21
000285654 7001_ $$aAfflerbach, Ann-Kristin$$b22
000285654 7001_ $$aEckhardt, Alicia$$b23
000285654 7001_ $$00000-0001-8823-0238$$aMünter, Daniel$$b24
000285654 7001_ $$aVerma, Archana$$b25
000285654 7001_ $$aStruve, Nina$$b26
000285654 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b27$$udkfz
000285654 7001_ $$0P:(DE-He78)a244aa021112b9002419791434bbc71c$$aRemke, Marc$$b28$$udkfz
000285654 7001_ $$00000-0002-1162-8771$$aNeumann, Julia E$$b29
000285654 7001_ $$00000-0002-5676-8102$$aKerl, Kornelius$$b30
000285654 7001_ $$00000-0002-8731-1121$$aSchüller, Ulrich$$b31
000285654 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-023-43564-w$$gVol. 14, no. 1, p. 7717$$n1$$p7717$$tNature Communications$$v14$$x2041-1723$$y2023
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