Gliomas are the most common CNS tumors in children and adolescents. Epigenetic analysis has become a growing analytical tool in pediatric brain tumor research to improve diagnostics and understand the molecular mechansims underlying their developmental progression. DNA methylation signatures together with integrated histopathology are now globally recognized diagnostic tools and are incorporated in the new guidelines of the WHO Classification of CNS tumors. We are looking at epigenetic modifications, such as DNA methylation patterns as well as histone modifications, which can alter gene expression. By identifying specific patterns of epigenetic changes in pediatric gliomas, we aim to develop new diagnostic tools and therapies to improve clinical management for children with these types of brain tumors. Our research has already yielded important insights into the biology of pediatric gliomas, and hold promise for the development of new effective treatments in the future.
Our Division plays a key role in the organization of the international precision oncology program INFORM (INdividualized therapy FOr Relapsed Malignancies in children) by coordinating the molecular analyses and interpretation of patient data in real-time. As such, we provide access to comprehensive molecular profiling for high-risk pediatric cancer patients across Europe. The INFORM family covers 13 European countries, is running in more than 100 pediatric oncology research centers and has enrolled over 2500 relapsed/refractory pediatric cancer patients with approximately half of all cases coming from our international partners. The first clinical impact analysis demonstrated survival benefit for patients with very high priority targets who were treated with a matching drug. The study has further advanced and successfully implemented an ex vivo personalized drug sensitivity profiling platform under real-world conditions adding a new level of functional information to clinical decision making. This routine analysis is now in the transition to being reimbursed by health insurances in Germany and helps establishing such sequencing and screening platforms in other countries.
MNP Int-R is a follow-up registry study of the previous MNP 2.0 study that investigated the principle of DNA methylation signatures as part of a combined histological and molecular tumor classification to better and more accurately diagnose pediatric brain tumors at the time of primary diagnosis. This paved the way to add molecular diagnostics, including DNA methylation profiling and targeted gene panel sequencing, into routine diagnostics of primary CNS tumors in children and adolescents and integrated reference pathology, radiology and molecular results into a multilayered tumor diagnosis. MNP Int-R will follow the high diagnostic standard in an international setting and make a large impact on clinical disease management. At the same time, the continuous collection and analysis of data helps to identify yet undiscovered tumor types and sub-types, and discover the biology behind very rare molecular-defined tumor classes. Further development and training of the DNA methylation-based classification system helps to improve the molecular parameters and shapes long-term the design of future therapeutic studies influencing personalized precision treatment and new target therapeutic approaches.
