Accurately classifying CNS tumors at the time of primary diagnosis into a distinct entity is crucial for selecting the optimal treatment strategy for each individual patient. The principle of using DNA methylation signatures as part of a combined histological and molecular tumor classification to improve diagnostic accuracy was investigated in the preceding study: Molecular Neuropathology 2.0 (MNP 2.0). This study made molecular diagnostics, including DNA methylation profiling and targeted gene panel sequencing, accessible to all children diagnosed with a primary CNS tumor and aimed to integrate reference pathology, radiology, and molecular results into one, multi-layered tumor diagnosis.

The current followup study MNP IntR aims to establish an international registry for molecular data generation and coordination in pediatric neurooncology. The areas in which molecular findings will increasingly impact upon clinical patient management are (i) risk stratification into clinical trials based on defined molecular markers(such as in the SIOP PNET 5MB) study, (ii) further testing and (re-)assessment of treatment strategies in case of discrepant neuropathological and molecular results, (iii) initiation of genetic counselling in case of relevant alterations detected in a patient’s germline (i.e. cancer predisposition syndrome), and (iv) identification of potential molecular alterations as a rationale for targeted treatment at the time of tumor progression/recurrence (or even at primary diagnosis for selected cases, e.g., BRAF mutations in high-grade glioma patients).