Show simple item record

dc.contributor.authorShah, V
dc.contributor.authorSherborne, AL
dc.contributor.authorWalker, BA
dc.contributor.authorJohnson, DC
dc.contributor.authorBoyle, EM
dc.contributor.authorEllis, S
dc.contributor.authorBegum, DB
dc.contributor.authorProszek, PZ
dc.contributor.authorJones, JR
dc.contributor.authorPawlyn, C
dc.contributor.authorSavola, S
dc.contributor.authorJenner, MW
dc.contributor.authorDrayson, MT
dc.contributor.authorOwen, RG
dc.contributor.authorHoulston, RS
dc.contributor.authorCairns, DA
dc.contributor.authorGregory, WM
dc.contributor.authorCook, G
dc.contributor.authorDavies, FE
dc.contributor.authorJackson, GH
dc.contributor.authorMorgan, GJ
dc.contributor.authorKaiser, MF
dc.date.accessioned2020-06-15T10:20:06Z
dc.date.issued2018-01
dc.identifier.citationLeukemia, 2018, 32 (1), pp. 102 - 110
dc.identifier.issn0887-6924
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3733
dc.identifier.eissn1476-5551
dc.identifier.doi10.1038/leu.2017.179
dc.description.abstractRobust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1.60 (P=4.77 × 10 -7 ), 1.74 (P=0.0005), 1.90 (P=0.0089), 2.10 (P=8.86 × 10 -14 ) and 1.68 (P=2.18 × 10 -14 ), respectively. Patients with 'double-hit' defined by co-occurrence of at least two adverse lesions have an especially poor prognosis with HRs for OS of 2.67 (P=8.13 × 10 -27 ) for all patients and 3.19 (P=1.23 × 10 -18 ) for intensively treated patients. Using comprehensive CNA and translocation profiling in Myeloma XI we also demonstrate a strong association between t(4;14) and BIRC2/BIRC3 deletion (P=8.7 × 10 -15 ), including homozygous deletion. Finally, we define distinct sub-groups of hyperdiploid MM, with either gain(1q21) and CCND2 overexpression (P<0.0001) or gain(11q25) and CCND1 overexpression (P<0.0001). Profiling multiple genetic lesions can identify MM patients likely to relapse early allowing stratification of treatment.
dc.formatPrint-Electronic
dc.format.extent102 - 110
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectMultiple Myeloma
dc.subjectNeoplasm Recurrence, Local
dc.subjectChromosome Aberrations
dc.subjectChromosome Deletion
dc.subjectTranslocation, Genetic
dc.subjectPrognosis
dc.subjectDisease-Free Survival
dc.subjectTransplantation, Autologous
dc.subjectProportional Hazards Models
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectClinical Trials, Phase III as Topic
dc.titlePrediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients.
dc.typeJournal Article
dcterms.dateAccepted2017-05-25
rioxxterms.versionofrecord10.1038/leu.2017.179
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfLeukemia
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/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/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
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/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.publication-statusPublished
pubs.volume32
pubs.embargo.termsNot known
icr.researchteamMyeloma Biology and Therapeuticsen_US
icr.researchteamCancer Genomicsen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorPawlyn, Charlotteen
dc.contributor.icrauthorJohnson, Daviden
dc.contributor.icrauthorKaiser, Martinen
dc.contributor.icrauthorHoulston, Richarden
dc.contributor.icrauthorShah, Vallarien


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0