An international team of researchers led by the Research Institute of the Children’s Cancer Center Hamburg and the KiTZ Hopp Children’s Cancer Center Heidelberg has created the world’s most comprehensive epigenetic atlas of mouse models of childhood cancer. The study, published in Nature Genetics, provides new insights into the development of brain tumors in children and opens up perspectives for more targeted therapies.

The study is based on 106 mouse models from 20 international laboratories, covering 31 different types of pediatric tumors. In addition, 18 new models for pediatric brain tumors were developed in Heidelberg. Childhood brain tumors such as high-grade gliomas or medulloblastomas are among the most aggressive cancers in childhood. Their molecular diversity complicates research and therapy. In particular, copy number changes – the absence or duplication of genetic segments – play a central role, but their exact function was previously unclear.

The analysis of DNA methylation showed a high agreement between the mouse models and human tumors. The composition of the immune cells in the tumor was also similar to the human situation. The researchers found that copy number changes do not occur randomly, but recur depending on the type of tumor. These patterns were observed in both the mouse models and in human patients, making the models suitable for studying human tumors. In addition, the tumors continue to develop in a targeted manner: Even after multiple transfers to new mice, the same genetic changes occur, which indicates controlled tumor development.

For the first time, the mouse models make it possible to study tumorigenesis in early stages, which are inaccessible in human patients. This could promote the development of more precise therapies that also take into account copy number changes. The models are also suitable for preclinical studies to test new treatment approaches.

The study, funded by the European Research Council (ERC) and the German Research Foundation (DFG), among others, is an example of the interlocking of basic research and clinical application. The atlas is available to the global research community and is already being used for new studies. The results lay the foundation for a more detailed understanding of childhood brain tumors and could improve the treatment of affected children in the long term.

Original Paper:

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. Nature Genetics (2025). DOI: 10.1038/s41588-025-02419-4

Editor: X-Press Journalistenbüro GbR

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