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dc.contributor.authorJohnson, DC
dc.contributor.authorLenive, O
dc.contributor.authorMitchell, J
dc.contributor.authorJackson, G
dc.contributor.authorOwen, R
dc.contributor.authorDrayson, M
dc.contributor.authorCook, G
dc.contributor.authorJones, JR
dc.contributor.authorPawlyn, C
dc.contributor.authorDavies, FE
dc.contributor.authorWalker, BA
dc.contributor.authorWardell, C
dc.contributor.authorGregory, WM
dc.contributor.authorCairns, D
dc.contributor.authorMorgan, GJ
dc.contributor.authorHoulston, RS
dc.contributor.authorHoulston, RS
dc.contributor.authorKaiser, MF
dc.date.accessioned2017-11-24T13:40:38Z
dc.date.issued2017-10
dc.identifier.citationBlood, 2017, 130 (14), pp. 1639 - 1643
dc.identifier.issn0006-4971
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/951
dc.identifier.eissn1528-0020
dc.identifier.doi10.1182/blood-2016-11-750612
dc.description.abstractRecent studies suggest that the evolutionary history of a cancer is important in forecasting clinical outlook. To gain insight into the clonal dynamics of multiple myeloma (MM) and its possible influence on patient outcomes, we analyzed whole exome sequencing tumor data for 333 patients from Myeloma XI, a UK phase 3 trial and 434 patients from the CoMMpass study, all of which had received immunomodulatory drug (IMiD) therapy. By analyzing mutant allele frequency distributions in tumors, we found that 17% to 20% of MM is under neutral evolutionary dynamics. These tumors are associated with poorer patient survival in nonintensively treated patients, which is consistent with the reduced therapeutic efficacy of microenvironment-modulating IMiDs. Our findings provide evidence that knowledge of the evolutionary history of MM has relevance for predicting patient outcomes and personalizing therapy.
dc.formatPrint-Electronic
dc.format.extent1639 - 1643
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectHumans
dc.subjectMultiple Myeloma
dc.subjectThalidomide
dc.subjectImmunosuppressive Agents
dc.subjectImmunologic Factors
dc.subjectPrognosis
dc.subjectGene Frequency
dc.subjectGenetic Drift
dc.subjectMutation
dc.subjectFemale
dc.subjectMale
dc.subjectKaplan-Meier Estimate
dc.subjectTumor Microenvironment
dc.subjectExome
dc.subjectLenalidomide
dc.titleNeutral tumor evolution in myeloma is associated with poor prognosis.
dc.typeJournal Article
dcterms.dateAccepted2017-08-07
rioxxterms.versionofrecord10.1182/blood-2016-11-750612
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2017-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBlood
pubs.issue14
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/Myeloma Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
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/Myeloma Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.publication-statusPublished
pubs.volume130
pubs.embargo.termsNot known
icr.researchteamMyeloma Biology and Therapeuticsen_US
icr.researchteamCancer Genomicsen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorPawlyn, Charlotteen
dc.contributor.icrauthorHoulston, Richarden
dc.contributor.icrauthorKaiser, Martinen


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