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Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/23209
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dc.contributor.authorHill, Rebecca Men_UK
dc.contributor.authorKuijper, Sanneen_UK
dc.contributor.authorLindsey, Janet Cen_UK
dc.contributor.authorPetrie, Kevinen_UK
dc.contributor.authorSchwalbe, Ed Cen_UK
dc.contributor.authorBarker, Karenen_UK
dc.contributor.authorBoult, Jessica K Ren_UK
dc.contributor.authorWilliamson, Danielen_UK
dc.contributor.authorAhmad, Zaien_UK
dc.contributor.authorHallsworth, Alberten_UK
dc.contributor.authorRyan, Sarra Len_UK
dc.contributor.authorPoon, Evonen_UK
dc.contributor.authorRobinson, Simon Pen_UK
dc.contributor.authorRuddle, Ruthen_UK
dc.contributor.authorRaynaud, Florence Ien_UK
dc.date.accessioned2016-05-19T23:59:54Z-
dc.date.available2016-05-19T23:59:54Z-
dc.date.issued2015-01-12en_UK
dc.identifier.urihttp://hdl.handle.net/1893/23209-
dc.description.abstractWe 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.en_UK
dc.language.isoenen_UK
dc.publisherElsevieren_UK
dc.relationHill 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.2014.11.002en_UK
dc.rightsThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).en_UK
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_UK
dc.titleCombined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable diseaseen_UK
dc.typeJournal Articleen_UK
dc.identifier.doi10.1016/j.ccell.2014.11.002en_UK
dc.identifier.pmid25533335en_UK
dc.citation.jtitleCancer Cellen_UK
dc.citation.issn1878-3686en_UK
dc.citation.issn1535-6108en_UK
dc.citation.volume27en_UK
dc.citation.issue1en_UK
dc.citation.spage72en_UK
dc.citation.epage84en_UK
dc.citation.publicationstatusPublisheden_UK
dc.type.statusVoR - Version of Recorden_UK
dc.author.emailkevin.petrie@stir.ac.uken_UK
dc.citation.date18/12/2014en_UK
dc.description.notesAdditional 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. Clifforden_UK
dc.contributor.affiliationNewcastle Universityen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationNewcastle Universityen_UK
dc.contributor.affiliationBiological and Environmental Sciencesen_UK
dc.contributor.affiliationNewcastle Universityen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationNewcastle Universityen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationNewcastle Universityen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.identifier.isiWOS:000347906900011en_UK
dc.identifier.scopusid2-s2.0-84922235074en_UK
dc.identifier.wtid573912en_UK
dc.contributor.orcid0000-0002-9805-9152en_UK
dcterms.dateAccepted2014-12-18en_UK
dc.date.filedepositdate2016-05-19en_UK
rioxxterms.apcnot requireden_UK
rioxxterms.typeJournal Article/Reviewen_UK
rioxxterms.versionVoRen_UK
local.rioxx.authorHill, Rebecca M|en_UK
local.rioxx.authorKuijper, Sanne|en_UK
local.rioxx.authorLindsey, Janet C|en_UK
local.rioxx.authorPetrie, Kevin|0000-0002-9805-9152en_UK
local.rioxx.authorSchwalbe, Ed C|en_UK
local.rioxx.authorBarker, Karen|en_UK
local.rioxx.authorBoult, Jessica K R|en_UK
local.rioxx.authorWilliamson, Daniel|en_UK
local.rioxx.authorAhmad, Zai|en_UK
local.rioxx.authorHallsworth, Albert|en_UK
local.rioxx.authorRyan, Sarra L|en_UK
local.rioxx.authorPoon, Evon|en_UK
local.rioxx.authorRobinson, Simon P|en_UK
local.rioxx.authorRuddle, Ruth|en_UK
local.rioxx.authorRaynaud, Florence I|en_UK
local.rioxx.projectInternal Project|University of Stirling|https://isni.org/isni/0000000122484331en_UK
local.rioxx.freetoreaddate2016-05-19en_UK
local.rioxx.licencehttp://creativecommons.org/licenses/by/4.0/|2016-05-19|en_UK
local.rioxx.filenameHill et al_Cancer Cell_2015.pdfen_UK
local.rioxx.filecount1en_UK
local.rioxx.source1535-6108en_UK
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