Home > Publications database > Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures. > print

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100 1 _ |a Schoof, Melanie
|0 0000-0002-1373-8130
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245 _ _ |a Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures.
260 _ _ |a [London]
|c 2023
|b Nature Publishing Group UK
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520 _ _ |a Pediatric 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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650 _ 7 |a N-Myc Proto-Oncogene Protein
|2 NLM Chemicals
650 _ 7 |a MYCN protein, human
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Child
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a N-Myc Proto-Oncogene Protein: genetics
|2 MeSH
650 _ 2 |a N-Myc Proto-Oncogene Protein: metabolism
|2 MeSH
650 _ 2 |a Neuroblastoma: metabolism
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Glioma: genetics
|2 MeSH
650 _ 2 |a Mutation
|2 MeSH
650 _ 2 |a Gene Amplification
|2 MeSH
700 1 _ |a Godbole, Shweta
|0 0000-0002-5162-5233
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700 1 _ |a Albert, Thomas K
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700 1 _ |a Dottermusch, Matthias
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700 1 _ |a Walter, Carolin
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700 1 _ |a Ballast, Annika
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700 1 _ |a Qin, Nan
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700 1 _ |a Olivera, Marlena Baca
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700 1 _ |a Göbel, Carolin
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700 1 _ |a Neyazi, Sina
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700 1 _ |a Holdhof, Dörthe
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700 1 _ |a Kresbach, Catena
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700 1 _ |a Peter, Levke-Sophie
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700 1 _ |a Epplen, Gefion Dorothea
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700 1 _ |a Thaden, Vanessa
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700 1 _ |a Spohn, Michael
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700 1 _ |a Blattner-Johnson, Mirjam
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700 1 _ |a Modemann, Franziska
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700 1 _ |a Mynarek, Martin
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700 1 _ |a Rutkowski, Stefan
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700 1 _ |a Sill, Martin
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700 1 _ |a Varghese, Julian
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700 1 _ |a Afflerbach, Ann-Kristin
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700 1 _ |a Eckhardt, Alicia
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700 1 _ |a Münter, Daniel
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700 1 _ |a Verma, Archana
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700 1 _ |a Struve, Nina
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700 1 _ |a Jones, David
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700 1 _ |a Remke, Marc
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700 1 _ |a Neumann, Julia E
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700 1 _ |a Kerl, Kornelius
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700 1 _ |a Schüller, Ulrich
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773 _ _ |a 10.1038/s41467-023-43564-w
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