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Investigation of a global mouse methylome atlas reveals subtype-specific copy number alterations in pediatric cancer models

Copy number alterations (CNAs) are hallmarks of cancer, yet investigation of their oncogenic role has been hindered by technical limitations and missing model systems. Here we generated a genome-wide DNA methylation and CNA atlas of 106 genetic mouse models across 31 pediatric tumor types, including...

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Main Authors: Schoof, Melanie (Author) , Zheng, Tuyu (Author) , Sill, Martin (Author) , Imle, Roland (Author) , Cais, Alessia (Author) , Altendorf, Lea (Author) , Fürst, Alicia (Author) , Hofmann, Nina (Author) , Ernst, Kati (Author) , Vonficht, Dominik (Author) , Chan, Kenneth Chun-Ho (Author) , Holland-Letz, Tim (Author) , Postlmayr, Andreas (Author) , Shiraishi, Ryo (Author) , Wang, Wanchen (Author) , Morcavallo, Alaide (Author) , Spohn, Michael (Author) , Göbel, Carolin (Author) , Niesen, Judith (Author) , Peter, Levke-Sophie (Author) , Bourdeaut, Franck (Author) , Han, Zhi-Yan (Author) , Pei, Yanxin (Author) , Murad, Najiba (Author) , Swartling, Fredrik J. (Author) , Taylor, Jessica (Author) , Yadav, Monika (Author) , Gibson, Garrett R. (Author) , Gilbertson, Richard J. (Author) , Dottermusch, Matthias (Author) , Roy, Rajanya (Author) , Kerl, Kornelius (Author) , Glass, Rainer (Author) , Cheng, Jiying (Author) , Horstmann, Martin A. (Author) , Wolters-Eisfeld, Gerrit (Author) , Zhao, Haotian (Author) , Sturm, Dominik (Author) , Yadav, Viveka Nand (Author) , Chesler, Louis (Author) , Haas, Simon (Author) , Weiss, William A. (Author) , Northcott, Paul A. (Author) , Kutscher, Lena M. (Author) , Guerreiro Stucklin, Ana (Author) , Ayrault, Olivier (Author) , Neumann, Julia E. (Author) , Kawauchi, Daisuke (Author) , Jones, David T. W. (Author) , Pajtler, Kristian Wilfried (Author) , Banito, Ana (Author) , Pfister, Stefan (Author) , Schüller, Ulrich (Author) , Zuckermann, Marc (Author)
Format: Article (Journal)
Language:English
Published: January 2026
In: Nature genetics
Year: 2026, Volume: 58, Pages: 143-156, [1-18]
ISSN:1546-1718
DOI:10.1038/s41588-025-02419-4
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41588-025-02419-4
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41588-025-02419-4
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Author Notes:Melanie Schoof, Tuyu Zheng, Martin Sill, Roland Imle, Alessia Cais, Lea Altendorf, Alicia Fürst, Nina Hofmann, Kati Ernst, Dominik Vonficht, Kenneth Chun-Ho Chan, Tim Holland-Letz, Andreas Postlmayr, Ryo Shiraishi, Wanchen Wang, Alaide Morcavallo, Michael Spohn, Carolin Göbel, Judith Niesen, Levke-Sophie Peter, Franck Bourdeaut, Zhi-Yan Han, Yanxin Pei, Najiba Murad, Fredrik J. Swartling, Jessica Taylor, Monika Yadav, Garrett R. Gibson, Richard J. Gilbertson, Matthias Dottermusch, Rajanya Roy, Kornelius Kerl, Rainer Glass, Jiying Cheng, Martin A. Horstmann, Gerrit Wolters-Eisfeld, Haotian Zhao, Dominik Sturm, Viveka Nand Yadav, Louis Chesler, Simon Haas, William A. Weiss, Paul A. Northcott, Lena M. Kutscher, Ana Guerreiro Stucklin, Olivier Ayrault, Julia E. Neumann, Daisuke Kawauchi, David T. W. Jones, Kristian Pajtler, Ana Banito, Stefan M. Pfister, Ulrich Schüller & Marc Zuckermann
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Summary:Copy number alterations (CNAs) are hallmarks of cancer, yet investigation of their oncogenic role has been hindered by technical limitations and missing model systems. Here we generated a genome-wide DNA methylation and CNA atlas of 106 genetic mouse models across 31 pediatric tumor types, including 18 new models for pediatric glioma. We demonstrated their epigenetic resemblance to human disease counterparts and identified entity-specific patterns of immune infiltration. We discovered that mouse tumors harbor highly recurrent CNA signatures that occur distinctly based on the tumor subgroup and driving oncogene and showed that these CNAs share syntenic regions with the matching human tumor types, thereby revealing a conserved but previously underappreciated role in subgroup-specific tumorigenesis that can be analyzed using the presented models. Our study provides insights into globally available mouse models for pediatric solid cancers and enables access to functional CNA interrogation, with the potential to unlock new translational targets in pediatric cancers.
Item Description:Online veröffentlicht: 11. Dezember 2025
Gesehen am 20.02.2026
Physical Description:Online Resource
ISSN:1546-1718
DOI:10.1038/s41588-025-02419-4

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