Integrative Functional Genomics of Recurrent Childhood Medulloblastoma

Medulloblastoma (MB), the most common malignant brain tumor in children, often confers a poor prognosis, especially for patients who have cancer relapse. Tumor relapse is among the most powerful predictors of prognosis despite therapeutic intervention and clinical trial enrollment in patients with MB. Little is known about the molecular genetics of MB relapse and although MB subgroup status remains stable at relapse, the degree that the genetics is altered between these disease states is unclear. Other entities have proposed that MB relapses spawn from rare, treatment-resistant subclones present in the primary tumor, but this has yet to be substantiated. Since MB clinical trials will begin to evaluate targeted therapies in patients with relapsed MB, understanding how MB relapses are related to the primary tumors from which they arise is integral to the success of therapies. Systematic, genome-wide studies designed to effectively investigate the molecular relationship between diagnostic and relapsed MB in a sizable cohort are needed. This project seeks to do just that by utilizing tumor samples and access to the Pediatric Brain Tumor Atlas, both provided by the Children’s Brain Tumor Network.