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dc.contributor.authorHill, RM
dc.contributor.authorKuijper, S
dc.contributor.authorLindsey, JC
dc.contributor.authorPetrie, K
dc.contributor.authorSchwalbe, EC
dc.contributor.authorBarker, K
dc.contributor.authorBoult, JKR
dc.contributor.authorWilliamson, D
dc.contributor.authorAhmad, Z
dc.contributor.authorHallsworth, A
dc.contributor.authorRyan, SL
dc.contributor.authorPoon, E
dc.contributor.authorRobinson, SP
dc.contributor.authorRuddle, R
dc.contributor.authorRaynaud, FI
dc.contributor.authorHowell, L
dc.contributor.authorKwok, C
dc.contributor.authorJoshi, A
dc.contributor.authorNicholson, SL
dc.contributor.authorCrosier, S
dc.contributor.authorEllison, DW
dc.contributor.authorWharton, SB
dc.contributor.authorRobson, K
dc.contributor.authorMichalski, A
dc.contributor.authorHargrave, D
dc.contributor.authorJacques, TS
dc.contributor.authorPizer, B
dc.contributor.authorBailey, S
dc.contributor.authorSwartling, FJ
dc.contributor.authorWeiss, WA
dc.contributor.authorChesler, L
dc.contributor.authorClifford, SC
dc.date.accessioned2020-08-05T12:53:13Z
dc.date.issued2015-01
dc.identifier.citationCancer cell, 2015, 27 (1), pp. 72 - 84
dc.identifier.issn1535-6108
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3904
dc.identifier.eissn1878-3686
dc.identifier.doi10.1016/j.ccell.2014.11.002
dc.description.abstractWe 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 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.
dc.formatPrint-Electronic
dc.format.extent72 - 84
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectMedulloblastoma
dc.subjectCerebellar Neoplasms
dc.subjectNeoplasms, Experimental
dc.subjectNeoplasm Recurrence, Local
dc.subjectProto-Oncogene Proteins c-myc
dc.subjectOncogene Proteins
dc.subjectNuclear Proteins
dc.subjectAntineoplastic Agents
dc.subjectSignal Transduction
dc.subjectGene Amplification
dc.subjectMutation
dc.subjectMolecular Sequence Data
dc.subjectAdolescent
dc.subjectAdult
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectFemale
dc.subjectMale
dc.subjectTumor Suppressor Protein p53
dc.subjectYoung Adult
dc.subjectN-Myc Proto-Oncogene Protein
dc.titleCombined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.
dc.typeJournal Article
dcterms.dateAccepted2014-11-05
rioxxterms.versionofrecord10.1016/j.ccell.2014.11.002
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2015-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer cell
pubs.issue1
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.publication-statusPublished
pubs.volume27
pubs.embargo.termsNot known
icr.researchteamClinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)en_US
icr.researchteamPaediatric Solid Tumour Biology and Therapeuticsen_US
icr.researchteamPre-Clinical MRIen_US
dc.contributor.icrauthorRaynaud, Florenceen
dc.contributor.icrauthorPetrie, Kevinen
dc.contributor.icrauthorRobinson, Simonen
dc.contributor.icrauthorChesler, Louisen
dc.contributor.icrauthorBoult, Jessicaen
dc.contributor.icrauthorKwok, Colinen
dc.contributor.icrauthorPoon, Evonen


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