The Hopp Children's Cancer Center Heidelberg (KiTZ) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD), and Heidelberg University (Uni HD).
A particular challenge with pediatric tumors is their enormous diversity: each tumor has a different molecular structure. “We know that so-called copy number alterations—i.e., the absence or duplication of larger sections of genetic material—also play an important role in childhood cancers,” says Marc Zuckermann, research group leader at the Hopp Children's Cancer Center Heidelberg (KiTZ) and the German Cancer Research Center (DKFZ). “But their exact function in tumor development was largely unknown until now because we lacked the right tools to study them.”
As the study now shows, mouse models can be used in the future to investigate such changes in copy number. Although such changes are typical in many tumors, little is known about the role they play in the course of the disease and when they arise. The reason: human tumor material from early stages of the disease is hardly available.
In the present study, the scientists analyzed tissue samples from 106 different mouse models for pediatric tumors – from brain tumors to soft tissue sarcomas. The study thus combines data from 20 research laboratories worldwide and represents the most comprehensive epigenetic reference for pediatric tumor models to date. In addition, the team in Heidelberg has developed 18 new models for particularly aggressive pediatric brain tumors.
“This global collaboration was crucial,” explains Ulrich Schüller, director of the Children's Cancer Center Hamburg research institute. “Only by pooling global expertise were we able to create this comprehensive atlas.”
When comparing DNA methylation patterns and copy number changes in tumors in mice and human tumors, striking parallels between mice and humans were found. It was particularly surprising that these patterns occur strictly tumor-specifically, depending on the tumor type, subtype, and the cancer gene that is activated in each case. Many of these genetic and epigenetic patterns also correspond to the respective human tumors, as the study shows. The researchers therefore assume that these genetic changes are equally fundamental drivers of tumor development in mice and humans and can now be investigated for the first time during development using the appropriate mouse models.
“Our work lays the foundation that will allow us to systematically investigate the role of copy number changes in early tumor development for the first time,” says Zuckermann. “This could lead to completely new treatment strategies for children with cancer in the future.”
Original publication:
Schoof, M., Zheng, T., Sill, M. et al. Investigation of a global mouse methylome atlas reveals subtype-specific copy number alterations in pediatric cancer models. In: Nature Genetics (online publication December 11, 2025). DOI: 10.1038/s41588-025-02419-4
