An Animal Model of MYC-Driven Medulloblastoma

作者：Pei Yanxin; Moore Colin E; Wang Jun; Tewari Alok K; Eroshkin Alexey; Cho Yoon Jae; Witt Hendrik; Korshunov Andrey; Read Tracy Ann; Sun Julia L; Schmitt Earlene M; Miller C Ryan; Buckley Anne F; McLendon Roger E; Westbrook Thomas F; Northcott Paul A; Taylor Michael D; Pfister Stefan M; Febbo Phillip G; Wechsler Reya Robert J^*

来源：Cancer Cell, 2012, 21(2): 155-167.

DOI：10.1016/j.ccr.2011.12.021

Medulloblastoma (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.

• 出版日期2012-2-14