An Animal Model of MYC-Driven Medulloblastoma

SummaryMedulloblastoma (MB) is the most common malignant brain tumor in children. Patients whose tumors exhibit overexpression or amplification of the MYC oncogene (c-MYC) usually have an extremely poor prognosis, but there are no animal models of this subtype of the disease. Here, we show that cerebellar stem cells expressing Myc and mutant Trp53 (p53) generate aggressive tumors following orthotopic transplantation. These tumors consist of large, pleiomorphic cells and resemble human MYC-driven MB at a molecular level. Notably, antagonists of PI3K/mTOR signaling, but not Hedgehog signaling, inhibit growth of tumor cells. These findings suggest that cerebellar stem cells can give rise to MYC-driven MB and identify a novel model that can be used to test therapies for this devastating disease.

► Myc promotes proliferation of cerebellar stem cells in vitro
► Mutant p53 cooperates with Myc to transform stem cells into tumors
► Tumors resulting from Myc and mutant p53 resemble human MYC-driven MB
► Tumors are inhibited by PI3K/mTOR antagonists