> Details

Schoof, Melanie; Godbole, Shweta; Albert, Thomas K.; Dottermusch, Matthias; Walter, Carolin; Ballast, Annika; Qin, Nan; Olivera, Marlena Baca; Göbel, Carolin; Neyazi, Sina; Holdhof, Dörthe; Kresbach, Catena; Peter, Levke-Sophie; Epplen, Gefion Dorothea; Thaden, Vanessa; Spohn, Michael; Blattner-Johnson, Mirjam; Modemann, Franziska; Mynarek, Martin; Rutkowski, Stefan; Sill, Martin; Varghese, Julian; Afflerbach, Ann-Kristin; Eckhardt, Alicia; [...]

Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures

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  • Media type: E-Article
  • Title: Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures
  • Contributor: Schoof, Melanie; Godbole, Shweta; Albert, Thomas K.; Dottermusch, Matthias; Walter, Carolin; Ballast, Annika; Qin, Nan; Olivera, Marlena Baca; Göbel, Carolin; Neyazi, Sina; Holdhof, Dörthe; Kresbach, Catena; Peter, Levke-Sophie; Epplen, Gefion Dorothea; Thaden, Vanessa; Spohn, Michael; Blattner-Johnson, Mirjam; Modemann, Franziska; Mynarek, Martin; Rutkowski, Stefan; Sill, Martin; Varghese, Julian; Afflerbach, Ann-Kristin; Eckhardt, Alicia; [...]
  • imprint: Springer Science and Business Media LLC, 2023
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/s41467-023-43564-w
  • ISSN: 2041-1723
  • Keywords: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying <jats:italic>MYCN</jats:italic> amplifications, <jats:italic>TP53</jats:italic> 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 <jats:italic>hGFAP-cre::Trp53</jats:italic><jats:sup><jats:italic>Fl/Fl</jats:italic></jats:sup><jats:italic>::lsl-MYCN</jats:italic> 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.</jats:p>
  • Access State: Open Access