An Animal Model of MYC-Driven Medulloblastoma

详细信息    查看全文

• 作者：Yanxin Pei¹ ; Colin  ; E. Moore¹ ; Jun Wang¹ ; Alok  ; K. Tewari³ ; Alexey Eroshkin² ; Yoon-Jae Cho⁴ ; Hendrik Witt⁵ ; Andrey Korshunov⁵ ; Tracy-Ann Read⁶ ; Julia  ; L. Sun⁷ ; ⁸ ; Earlene  ; M. Schmitt⁹ ; C.  ; Ryan Miller¹¹ ; Anne  ; F. Buckley⁸ ; Roger  ; E. McLendon⁸ ; Thomas  ; F. Westbrook⁹ ; ¹⁰ ; Paul  ; A. Northcott¹² ; Michael  ; D. Taylor¹² ; Stefan  ; M. Pfister⁵ ; Phillip  ; G. Febbo³ ; Robert  ; J. Wechsler-Reya¹ ; ⁷ ; ^{rwreya@sanfordburnham.org}
• 刊名：Cancer Cell
• 出版年：2012
• 出版时间：14 February 2012
• 年：2012
• 卷：21
• 期：2
• 页码：155-167
• 全文大小：2278 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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.