Document Type

Article

Publication Date

1-2026

Identifier

DOI: 10.1038/s41588-025-02419-4; PMCID: PMC12807868

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.

Journal Title

Nature genetics

Volume

58

Issue

1

First Page

143

Last Page

156

MeSH Keywords

Animals; Mice; DNA Copy Number Variations; Humans; DNA Methylation; Neoplasms; Disease Models, Animal; Epigenome; Epigenesis, Genetic; Child; Gene Expression Regulation, Neoplastic

PubMed ID

41381884

Keywords

DNA Copy Number Variations; DNA Methylation; Neoplasms; Animal Disease Models; Epigenome; Epigenesis, Genetic; Neoplastic Gene Expression Regulation

Comments

Grants and funding

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Publisher's Link: https://www.nature.com/articles/s41588-025-02419-4

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