PROJECT SUMMARY The Molecular Characterization Trial (MCT) is the source of biospecimen and data resources for the ROBIN Center. As such, its success is paramount to the success of the entire initiative, and strategies that expedite the acquisition of these essential resources will accelerate the timeframe in which they are made available for all the innovative work performed in the Research Projects and Cores. The Harvard/UCSF ROBIN has chosen for its theme the study of pediatric malignancies as the optimal setting for in depth investigation into the impact of heterogeneity, in both its tumor cell intrinsic and extrinsic manifestations, on radiation responses. The MCT will achieve these goals via the following Aims: Aim 1: Coordinate the collection of biospecimens and clinical data from cooperative group studies for use in ROBIN studies. The MCT will leverage two ongoing trials: Pacific Pediatric Neuro-Oncology Consortium PNOC023 for diffuse midline glioma (DMG), and Children’s Oncology Group (COG) ANBL1531 for neuroblastoma (NBL). The study chairs for each trial are co- leads of the MCT and Project 2, respectively. As a novel feature of the MCT, matched pairs of tumor samples will be available from subjects who underwent pre-treatment biopsies and subsequently had post-treatment surgical (NBL) or post-mortem (DMG) tissues obtained via established protocols. The ROBIN investigators will also leverage additional resources that are uniquely available to them, including a collection of thirty DMG tumor samples that are distinct from those obtained on the PNOC023 study and already in hand. The MCT will also bolster an aim on late effects by obtaining blood samples and clinical data from the COG Late Effects after High-Risk Neuroblastoma (LEAHRN) study, which includes 24 long-term survivors previously treated with the radiopharmaceutical 131I-MIBG. Aim 2: Manage the regulatory aspects of the MCT, including site protocols for collection of protected health information (PHI) and biospecimens in institutional biorepositories. Clinical research and data coordinators will work with site leads at both Dana-Farber/Harvard Cancer Center and UCSF to ensure rigorous and timely submission of study protocols, amendments, and continuing reviews so that the work can steadfastly proceed. Also, because all PHI will flow through the MCT, which provides de- identified resources to other ROBIN components, this will minimize risks to subject confidentiality. Aim 3: Maintain standard operating procedures for processing and analyzing tumor, blood and CSF samples and storing incoming and resultant high-dimensional data. Given the vast amounts of data involved, and the intricate assays being performed, it is essential that the work is performed in a harmonized way to maintain rigor and reproducibility. The MCT will rely on the combined expertise within the Clinical Artificial Intelligence and Imaging Core and the Molecular Data Science and Advanced Dosimetry Core to ensure ...