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dc.contributor.authorShah, Ven_US
dc.contributor.authorJohnson, DCen_US
dc.contributor.authorSherborne, ALen_US
dc.contributor.authorEllis, Sen_US
dc.contributor.authorAldridge, FMen_US
dc.contributor.authorHoward-Reeves, Jen_US
dc.contributor.authorBegum, Fen_US
dc.contributor.authorPrice, Aen_US
dc.contributor.authorKendall, Jen_US
dc.contributor.authorChiecchio, Len_US
dc.contributor.authorSavola, Sen_US
dc.contributor.authorJenner, MWen_US
dc.contributor.authorDrayson, MTen_US
dc.contributor.authorOwen, RGen_US
dc.contributor.authorGregory, WMen_US
dc.contributor.authorMorgan, GJen_US
dc.contributor.authorDavies, FEen_US
dc.contributor.authorHoulston, RSen_US
dc.contributor.authorCook, Gen_US
dc.contributor.authorCairns, DAen_US
dc.contributor.authorJackson, Gen_US
dc.contributor.authorKaiser, MFen_US
dc.contributor.authorNational Cancer Research Institute Haematology Clinical Studies Groupen_US
dc.date.accessioned2020-11-17T11:04:37Z
dc.date.issued2018-12en_US
dc.identifier.citationBlood, 2018, 132 (23), pp. 2465 - 2469en_US
dc.identifier.issn0006-4971en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4230
dc.identifier.eissn1528-0020en_US
dc.identifier.doi10.1182/blood-2018-06-857250en_US
dc.description.abstractMultiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts (P < .001) and increased lactate dehydrogenase (P < .001), as well as a higher frequency of features indicative of genomic instability, del(13q) (P = .002) or del(1p) (P = .006). Biallelic TP53 loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal TP53 deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies.en_US
dc.formatPrint-Electronicen_US
dc.format.extent2465 - 2469en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectNational Cancer Research Institute Haematology Clinical Studies Groupen_US
dc.subjectHumansen_US
dc.subjectMultiple Myelomaen_US
dc.subjectGenomic Instabilityen_US
dc.subjectDisease-Free Survivalen_US
dc.subjectSurvival Rateen_US
dc.subjectGene Deletionen_US
dc.subjectGene Dosageen_US
dc.subjectFemaleen_US
dc.subjectMaleen_US
dc.subjectTumor Suppressor Protein p53en_US
dc.titleSubclonal TP53 copy number is associated with prognosis in multiple myeloma.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-10-03en_US
rioxxterms.versionofrecord10.1182/blood-2018-06-857250en_US
rioxxterms.licenseref.startdate2018-12en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBlooden_US
pubs.issue23en_US
pubs.notesNot knownen_US
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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.publication-statusPublisheden_US
pubs.volume132en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMolecular & Population Geneticsen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorKaiser, Martinen_US
dc.contributor.icrauthorJohnson, Daviden_US
dc.contributor.icrauthorHoulston, Richarden_US
dc.contributor.icrauthorShah, Vallarien_US


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