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@ARTICLE{Schoof:285654,
author = {M. Schoof and S. Godbole and T. K. Albert and M.
Dottermusch and C. Walter and A. Ballast and N. Qin$^*$ and
M. B. Olivera$^*$ and C. Göbel and S. Neyazi and D. Holdhof
and C. Kresbach and L.-S. Peter and G. D. Epplen and V.
Thaden and M. Spohn and M. Blattner-Johnson$^*$ and F.
Modemann and M. Mynarek and S. Rutkowski and M. Sill$^*$ and
J. Varghese and A.-K. Afflerbach and A. Eckhardt and D.
Münter and A. Verma and N. Struve and D. Jones$^*$ and M.
Remke$^*$ and J. E. Neumann and K. Kerl and U. Schüller},
title = {{M}ouse models of pediatric high-grade gliomas with {MYCN}
amplification reveal intratumoral heterogeneity and lineage
signatures.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2023-02477},
pages = {7717},
year = {2023},
abstract = {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.},
keywords = {Humans / Child / Mice / Animals / N-Myc Proto-Oncogene
Protein: genetics / N-Myc Proto-Oncogene Protein: metabolism
/ Neuroblastoma: metabolism / Disease Models, Animal /
Glioma: genetics / Mutation / Gene Amplification / N-Myc
Proto-Oncogene Protein (NLM Chemicals) / MYCN protein, human
(NLM Chemicals)},
cin = {B360 / B062 / HD01 / ED01},
ddc = {500},
cid = {I:(DE-He78)B360-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)ED01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38001143},
pmc = {pmc:PMC10673884},
doi = {10.1038/s41467-023-43564-w},
url = {https://inrepo02.dkfz.de/record/285654},
}