Author/Authors :
Pei، نويسنده , , Yanxin and Moore، نويسنده , , Colin E. and Wang، نويسنده , , Jun and Tewari، نويسنده , , Alok K. and Eroshkin، نويسنده , , Alexey and Cho، نويسنده , , Yoon-Jae and Witt، نويسنده , , Hendrik and Korshunov، نويسنده , , Andrey and Read، نويسنده , , Tracy-Ann and Sun، نويسنده , , Julia L. and Schmitt، نويسنده , , Earlene M. and Miller، نويسنده , , C. Ryan and Buckley، نويسنده , , Anne F. and McLendon، نويسنده , , Roger E. and Westbrook، نويسنده , , Thomas F. and Northcott، نويسنده , , Paul A. and Taylor، نويسنده , , Michael D. and Pfister، نويسنده , , Stefan M. and Febbo، نويسنده , , Phillip G. and Wechsler-Reya، نويسنده , , Robert J.، نويسنده ,
Abstract :
Summary
oblastoma (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.
