International Molecular Neuropathology Registry (MNP Int-R)

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).

The MNP Int-R study will maintain the high diagnostic standard through providing comprehensive molecular diagnostics in newly diagnosed pediatric CNS tumor patients. The registry facilitates analysis of emerging patterns and new insights into tumor types and subtypes, their biology, and relation to each other, as well as the discovery of increasingly rare molecularly-defined CNS tumor classes. It allows to make CNS tumor classification by DNA methylation more robust and comprehensive by acquisition of clinically well-annotated molecular data and iterative re-training of the DNA methylation-based classification system. The continuous collection of molecular data in a central repository allows for population-based assessment of the frequency of any given molecular parameter, which is of great importance for the design of future therapeutic studies in the era of molecularly-informed clinical trials and with increasing availability of targeted therapeutic approaches. The registry also builds the basis for providing expertise to clinicians, patients/parents, and scientists seeking advice in interpreting molecular results.

All molecular analyses are being performed in close collaboration with the Clinical Cooperation Unit Neuropathology and the Section Molecular Neuropathology.

The MNP IntR study is funded by the German Childhood Cancer Foundation and performed in collaboration with the HIT Network of the German Society of Pediatric Oncology and Hematology (GPOH).

The MNP IntR study is open to all pediatric patients (≤ 21 years) at the time of primary diagnosis of a CNS tumor. Registration is carried out through treating pediatric oncologists in cooperation with responsible neuropathologists. To register your patient, please obtain informed consent and send a completed registration and shipment form to the appropriate neuropathological reference center (or in exceptions directly to the Dept. of Neuropathology Heidelberg). If you have any questions, please contact Dr. Dominik Sturm (via mnp(at)dkfz.de).