PROJECT SUMMARY In this effort, we will analyze clinically-annotated tumor samples from 50 GBM patients at initial diagnosis and at time of recurrence (50 “pairs”). We will perform single cell transcriptomic analyses at baseline and at recurrence, integrating cellular, molecular and phenotypic measurements with detailed clinical annotation, and histological and radiographic measurements to resolve the critical features that drive tumor evolution and disease progression. We will achieve this through a consortium of NCI Cancer Centers, and this will enable us to optimize statistical robustness and capture the extensive heterogeneity of the disease.