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http://hdl.handle.net/1893/23209| Appears in Collections: | Biological and Environmental Sciences Journal Articles |
| Title: | Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease |
| Author(s): | Hill, Rebecca M Kuijper, Sanne Lindsey, Janet C Petrie, Kevin Schwalbe, Ed C Barker, Karen Boult, Jessica K R Williamson, Daniel Ahmad, Zai Hallsworth, Albert Ryan, Sarra L Poon, Evon Robinson, Simon P Ruddle, Ruth Raynaud, Florence I |
| Contact Email: | kevin.petrie@stir.ac.uk |
| Issue Date: | 12-Jan-2015 |
| Date Deposited: | 19-May-2016 |
| Citation: | Hill RM, Kuijper S, Lindsey JC, Petrie K, Schwalbe EC, Barker K, Boult JKR, Williamson D, Ahmad Z, Hallsworth A, Ryan SL, Poon E, Robinson SP, Ruddle R & Raynaud FI (2015) Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease. Cancer Cell, 27 (1), pp. 72-84. https://doi.org/10.1016/j.ccell.2014.11.002 |
| Abstract: | We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. CombinedMYCfamily amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development ofTrp53inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. |
| DOI Link: | 10.1016/j.ccell.2014.11.002 |
| Rights: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
| Notes: | Additional co-authors: Louise Howell, Colin Kwok, Abhijit Joshi, Sarah Leigh Nicholson, Stephen Crosier, David W. Ellison, Stephen B. Wharton, Keith Robson, Antony Michalski, Darren Hargrave, Thomas S. Jacques, Barry Pizer, Simon Bailey, Fredrik J. Swartling, William A. Weiss, Louis Chesler, Steven C. Clifford |
| Licence URL(s): | http://creativecommons.org/licenses/by/4.0/ |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Hill et al_Cancer Cell_2015.pdf | Fulltext - Published Version | 6.57 MB | Adobe PDF | View/Open |
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