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

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Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures. / 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; Münter, Daniel; Verma, Archana; Struve, Nina; Jones, David T W; Remke, Marc; Neumann, Julia E; Kerl, Kornelius; Schüller, Ulrich.

In: NAT COMMUN, Vol. 14, No. 1, 24.11.2023, p. 7717.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schoof, M, Godbole, S, Albert, TK, Dottermusch, M, Walter, C, Ballast, A, Qin, N, Olivera, MB, Göbel, C, Neyazi, S, Holdhof, D, Kresbach, C, Peter, L-S, Epplen, GD, Thaden, V, Spohn, M, Blattner-Johnson, M, Modemann, F, Mynarek, M, Rutkowski, S, Sill, M, Varghese, J, Afflerbach, A-K, Eckhardt, A, Münter, D, Verma, A, Struve, N, Jones, DTW, Remke, M, Neumann, JE, Kerl, K & Schüller, U 2023, 'Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures', NAT COMMUN, vol. 14, no. 1, pp. 7717. https://doi.org/10.1038/s41467-023-43564-w

APA

Schoof, M., Godbole, S., Albert, T. K., Dottermusch, M., Walter, C., Ballast, A., Qin, N., Olivera, M. B., Göbel, C., Neyazi, S., Holdhof, D., Kresbach, C., Peter, L-S., Epplen, G. D., Thaden, V., Spohn, M., Blattner-Johnson, M., Modemann, F., Mynarek, M., ... Schüller, U. (2023). Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures. NAT COMMUN, 14(1), 7717. https://doi.org/10.1038/s41467-023-43564-w

Vancouver

Schoof M, Godbole S, Albert TK, Dottermusch M, Walter C, Ballast A et al. Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures. NAT COMMUN. 2023 Nov 24;14(1):7717. https://doi.org/10.1038/s41467-023-43564-w

Bibtex

@article{db673c4be61f4fac952ffb90d0a3b55a,
title = "Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures",
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, Neuroblastoma/metabolism, Disease Models, Animal, Glioma/genetics, Mutation, Gene Amplification",
author = "Melanie Schoof and Shweta Godbole and Albert, {Thomas K} and Matthias Dottermusch and Carolin Walter and Annika Ballast and Nan Qin and Olivera, {Marlena Baca} and Carolin G{\"o}bel and Sina Neyazi and D{\"o}rthe Holdhof and Catena Kresbach and Levke-Sophie Peter and Epplen, {Gefion Dorothea} and Vanessa Thaden and Michael Spohn and Mirjam Blattner-Johnson and Franziska Modemann and Martin Mynarek and Stefan Rutkowski and Martin Sill and Julian Varghese and Ann-Kristin Afflerbach and Alicia Eckhardt and Daniel M{\"u}nter and Archana Verma and Nina Struve and Jones, {David T W} and Marc Remke and Neumann, {Julia E} and Kornelius Kerl and Ulrich Sch{\"u}ller",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
month = nov,
day = "24",
doi = "10.1038/s41467-023-43564-w",
language = "English",
volume = "14",
pages = "7717",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures

AU - Schoof, Melanie

AU - Godbole, Shweta

AU - Albert, Thomas K

AU - Dottermusch, Matthias

AU - Walter, Carolin

AU - Ballast, Annika

AU - Qin, Nan

AU - Olivera, Marlena Baca

AU - Göbel, Carolin

AU - Neyazi, Sina

AU - Holdhof, Dörthe

AU - Kresbach, Catena

AU - Peter, Levke-Sophie

AU - Epplen, Gefion Dorothea

AU - Thaden, Vanessa

AU - Spohn, Michael

AU - Blattner-Johnson, Mirjam

AU - Modemann, Franziska

AU - Mynarek, Martin

AU - Rutkowski, Stefan

AU - Sill, Martin

AU - Varghese, Julian

AU - Afflerbach, Ann-Kristin

AU - Eckhardt, Alicia

AU - Münter, Daniel

AU - Verma, Archana

AU - Struve, Nina

AU - Jones, David T W

AU - Remke, Marc

AU - Neumann, Julia E

AU - Kerl, Kornelius

AU - Schüller, Ulrich

N1 - © 2023. The Author(s).

PY - 2023/11/24

Y1 - 2023/11/24

N2 - 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.

AB - 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.

KW - Humans

KW - Child

KW - Mice

KW - Animals

KW - N-Myc Proto-Oncogene Protein/genetics

KW - Neuroblastoma/metabolism

KW - Disease Models, Animal

KW - Glioma/genetics

KW - Mutation

KW - Gene Amplification

U2 - 10.1038/s41467-023-43564-w

DO - 10.1038/s41467-023-43564-w

M3 - SCORING: Journal article

C2 - 38001143

VL - 14

SP - 7717

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -