Combined MYC and TP53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Ed Schwalbe
PROVIDER: E-GEOD-62626 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.
Hill Rebecca M RM Kuijper Sanne S Lindsey Janet C JC Petrie Kevin K Schwalbe Ed C EC Barker Karen K Boult Jessica K R JK Williamson Daniel D Ahmad Zai Z Hallsworth Albert A Ryan Sarra L SL Poon Evon E Robinson Simon P SP Ruddle Ruth R Raynaud Florence I FI Howell Louise L Kwok Colin C Joshi Abhijit A Nicholson Sarah Leigh SL Crosier Stephen S Ellison David W DW Wharton Stephen B SB Robson Keith K Michalski Antony A Hargrave Darren D Jacques Thomas S TS Pizer Barry B Bailey Simon S Swartling Fredrik J FJ Weiss William A WA Chesler Louis L Clifford Steven C SC
Cancer cell 20141218 1
We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family 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 of Trp53 inactivating mutations. Abrogation of p53 function in this ...[more]
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