dc.contributor.author | Hill, RM | |
dc.contributor.author | Kuijper, S | |
dc.contributor.author | Lindsey, JC | |
dc.contributor.author | Petrie, K | |
dc.contributor.author | Schwalbe, EC | |
dc.contributor.author | Barker, K | |
dc.contributor.author | Boult, JKR | |
dc.contributor.author | Williamson, D | |
dc.contributor.author | Ahmad, Z | |
dc.contributor.author | Hallsworth, A | |
dc.contributor.author | Ryan, SL | |
dc.contributor.author | Poon, E | |
dc.contributor.author | Robinson, SP | |
dc.contributor.author | Ruddle, R | |
dc.contributor.author | Raynaud, FI | |
dc.contributor.author | Howell, L | |
dc.contributor.author | Kwok, C | |
dc.contributor.author | Joshi, A | |
dc.contributor.author | Nicholson, SL | |
dc.contributor.author | Crosier, S | |
dc.contributor.author | Ellison, DW | |
dc.contributor.author | Wharton, SB | |
dc.contributor.author | Robson, K | |
dc.contributor.author | Michalski, A | |
dc.contributor.author | Hargrave, D | |
dc.contributor.author | Jacques, TS | |
dc.contributor.author | Pizer, B | |
dc.contributor.author | Bailey, S | |
dc.contributor.author | Swartling, FJ | |
dc.contributor.author | Weiss, WA | |
dc.contributor.author | Chesler, L | |
dc.contributor.author | Clifford, SC | |
dc.date.accessioned | 2020-08-05T12:53:13Z | |
dc.date.issued | 2015-01-12 | |
dc.identifier.citation | Cancer cell, 2015, 27 (1), pp. 72 - 84 | |
dc.identifier.issn | 1535-6108 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3904 | |
dc.identifier.eissn | 1878-3686 | |
dc.identifier.doi | 10.1016/j.ccell.2014.11.002 | |
dc.description.abstract | 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 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.format | Print-Electronic | |
dc.format.extent | 72 - 84 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Medulloblastoma | |
dc.subject | Cerebellar Neoplasms | |
dc.subject | Neoplasms, Experimental | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Proto-Oncogene Proteins c-myc | |
dc.subject | Oncogene Proteins | |
dc.subject | Nuclear Proteins | |
dc.subject | Antineoplastic Agents | |
dc.subject | Signal Transduction | |
dc.subject | Gene Amplification | |
dc.subject | Mutation | |
dc.subject | Molecular Sequence Data | |
dc.subject | Adolescent | |
dc.subject | Adult | |
dc.subject | Child | |
dc.subject | Child, Preschool | |
dc.subject | Infant | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Tumor Suppressor Protein p53 | |
dc.subject | Young Adult | |
dc.subject | N-Myc Proto-Oncogene Protein | |
dc.title | Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2014-11-05 | |
rioxxterms.versionofrecord | 10.1016/j.ccell.2014.11.002 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2015-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancer cell | |
pubs.issue | 1 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 27 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group) | |
icr.researchteam | Paediatric Solid Tumour Biology and Therapeutics | |
icr.researchteam | Pre-Clinical MRI | |
dc.contributor.icrauthor | Petrie, Kevin | |
dc.contributor.icrauthor | Boult, Jessica | |
dc.contributor.icrauthor | Poon, Evon | |
dc.contributor.icrauthor | Robinson, Simon | |
dc.contributor.icrauthor | Ruddle, Ruth | |
dc.contributor.icrauthor | Raynaud, Florence | |
dc.contributor.icrauthor | Kwok, Colin | |
dc.contributor.icrauthor | Chesler, Louis | |