THE DEVELOPMENT OF PATIENT-DERIVED MODELS OF PEDIATRIC BRAIN TUMORS

Abstract Brain tumors are still a major cause of morbidity and mortality in children, despite extensive research. An individualized therapy is warranted to combat the heterogeneity present in these tumors. Therefore, this study aims at developing patient-derived models from both low- and high-grade tumors. As such, the heterogeneity in these tumors can be further characterized and treatment sensitivities can be studied. All pediatric patients diagnosed with a brain tumor at the University Hospitals Leuven and receiving surgical intervention were included after informed consent. If sufficient tumoral material was available, a fresh tumor sample was collected during surgery. The sample was processed into dissociated cells, which were grown in culture in order to develop a patient-derived cell line (PDCL). Biomarker expression using a qPCR array was performed if growth beyond passage 3 was achieved. Established PDCLs were subsequently subjected to genomic and transcriptional profiling and cytotoxicity assays were performed to determine therapeutic sensitivities. Patient-derived xenografts (PDX) are developped in selected cases. 70 patients were included prospectively up until January 2022 and tumoral material was available for 50 of them. In total, 10 PDCLs could be generated (3 high-grade, 7 low-grade tumors), while 9 early cultures (3 high-grade, 6 low-grade) are still being expanded. qPCR and sequencing analysis confirm preservation of driving mutations. The high level of growth failures of the PDCLs can be explained by the high proportion of lower grade tumors included. One PDX model was generated. In conclusion, novel patient-derived models from pediatric brain tumors have been generated, which recapitulate the characteristics of the original tumor. The models are a valuable tool to study these tumors and the responses to different treatments. Further on, we will continue with the development of these models and the study of their therapeutic sensitivities. This will help further improving the understanding of these tumors.