Clonal selection drives genetic divergence of metastatic medulloblastoma

摘要: Medulloblastoma, the most common malignant paediatric brain tumour, arises in cerebellum and disseminates through cerebrospinal fluid leptomeningeal space to coat spinal cord. Dissemination, a marker of poor prognosis, is found up 40% children at diagnosis time recurrence. Affected therefore are treated with radiation entire developing cord, followed by high-dose chemotherapy, ensuing deleterious effects on nervous system. The mechanisms dissemination poorly studied, medulloblastoma metastases have been assumed be biologically similar primary tumour. Here we show that both mouse human medulloblastoma, from an individual extremely each other but divergent matched Clonal genetic events can demonstrated restricted subclone suggesting only rare cells within tumour ability metastasize. Failure account for bicompartmental nature metastatic could major barrier development effective targeted therapies.