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

Schoof, Melanie; Zheng, Tuyu; Sill, Martin; Imle, Roland; Cais, Alessia; Altendorf, Lea; Fürst, Alicia; Hofmann, Nina; Ernst, Kati; Vonficht, Dominik; Chan, Kenneth Chun-Ho; Holland-Letz, Tim; Postlmayr, Andreas; Shiraishi, Ryo; Wang, Wanchen; Morcavallo, Alaide; Spohn, Michael; Göbel, Carolin; Niesen, Judith; Peter, Levke-Sophie; Bourdeaut, Franck; Han, Zhi-Yan; Pei, Yanxin; Murad, Najiba; Swartling, Fredrik J.; Taylor, Jessica; Yadav, Monika; Gibson, Garrett R.; Gilbertson, Richard J.; Dottermusch, Matthias; Roy, Rajanya; Kerl, Kornelius; Glass, Rainer; Cheng, Jiying; Horstmann, Martin A.; Wolters-Eisfeld, Gerrit; Zhao, Haotian; Sturm, Dominik; Yadav, Viveka Nand; Chesler, Louis; Haas, Simon; Weiss, William A.; Northcott, Paul A; Kutscher, Lena M.; Guerreiro Stucklin, Ana; Ayrault, Olivier; Neumann, Julia E.; Kawauchi, Daisuke; Jones, David T.W.; Pajtler, Kristian; Banito, Ana; Pfister, Stefan M.; Schüller, Ulrich; Zuckermann, Marc

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

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Item Type:	Article
Title:	Investigation of a global mouse methylome atlas reveals subtype-specific copy number alterations in pediatric cancer models
Creators Name:	Schoof, Melanie, Zheng, Tuyu, Sill, Martin, Imle, Roland, Cais, Alessia, Altendorf, Lea, Fürst, Alicia, Hofmann, Nina, Ernst, Kati, Vonficht, Dominik, Chan, Kenneth Chun-Ho, Holland-Letz, Tim, Postlmayr, Andreas, Shiraishi, Ryo, Wang, Wanchen, Morcavallo, Alaide, Spohn, Michael, Göbel, Carolin, Niesen, Judith, Peter, Levke-Sophie, Bourdeaut, Franck, Han, Zhi-Yan, Pei, Yanxin, Murad, Najiba, Swartling, Fredrik J., Taylor, Jessica, Yadav, Monika, Gibson, Garrett R., Gilbertson, Richard J., Dottermusch, Matthias, Roy, Rajanya, Kerl, Kornelius, Glass, Rainer, Cheng, Jiying, Horstmann, Martin A., Wolters-Eisfeld, Gerrit, Zhao, Haotian, Sturm, Dominik, Yadav, Viveka Nand, Chesler, Louis, Haas, Simon, Weiss, William A., Northcott, Paul A, Kutscher, Lena M., Guerreiro Stucklin, Ana, Ayrault, Olivier, Neumann, Julia E., Kawauchi, Daisuke, Jones, David T.W., Pajtler, Kristian, Banito, Ana, Pfister, Stefan M., Schüller, Ulrich and Zuckermann, Marc
Abstract:	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.
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Date:	11 December 2025
Official Publication:	https://doi.org/10.1038/s41588-025-02419-4
PubMed:	View item in PubMed
Related to:	URL URL Type https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275151 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123601 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE109381 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228091 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE188654 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE103348 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112699 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE120344 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE107263 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155471 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65888 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62625 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24628 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50824 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2426 External Dataset

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