Journal Article DKFZ-2025-02930

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

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2026
Macmillan Publishers Limited, part of Springer Nature London

Nature genetics 58(1), 143-156 () [10.1038/s41588-025-02419-4]
 GO

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.

Classification:

Note: #EA:B062#LA:B062# / 2026 Jan;58(1):143-156/ DKFZ-ZMBH Alliance

Contributing Institute(s):
  1. B062 Pädiatrische Neuroonkologie (B062)
  2. Pädiatrische Gliomforschung (B360)
  3. A010 Stammzellen und Krebs (A010)
  4. C060 Biostatistik (C060)
  5. Entwicklungsbiolog. Ursprünge pädiatrischer Krebserkrankungen (B430)
  6. NWG Weichteilsarkome (B380)
Research Program(s):
  1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025
Database coverage:
Medline ; OpenAccess ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2025-12-15, last modified 2026-02-12


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