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dc.contributor.authorLi, N
dc.contributor.authorJohnson, DC
dc.contributor.authorWeinhold, N
dc.contributor.authorStudd, JB
dc.contributor.authorOrlando, G
dc.contributor.authorMirabella, F
dc.contributor.authorMitchell, JS
dc.contributor.authorMeissner, T
dc.contributor.authorKaiser, M
dc.contributor.authorGoldschmidt, H
dc.contributor.authorHemminki, K
dc.contributor.authorMorgan, GJ
dc.contributor.authorHoulston, RS
dc.date.accessioned2017-01-04T13:52:32Z
dc.date.issued2016-11-24
dc.identifier.citationNature communications, 2016, 7 pp. 13656 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/362
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/ncomms13656
dc.description.abstractGenome-wide association studies have identified several risk loci for multiple myeloma (MM); however, the mechanisms by which they influence MM are unknown. Here by using genetic association data and functional characterization, we demonstrate that rs4487645 G>T, the most highly associated variant (P = 5.30 × 10<sup>-25</sup>), resides in an enhancer element 47 kb upstream of the transcription start site of c-Myc-interacting CDCA7L. The G-risk allele, associated with increased CDCA7L expression (P=1.95 × 10<sup>-36</sup>), increases IRF4 binding and the enhancer interacts with the CDCA7L promoter. We show that suppression of CDCA7L limits MM proliferation through apoptosis, and increased CDCA7L expression is associated with adverse patient survival. These findings implicate IRF4-mediated CDCA7L expression in MM biology and indicate how germline variation might confer susceptibility to MM.
dc.formatElectronic
dc.format.extent13656 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectMultiple Myeloma
dc.subjectGenetic Predisposition to Disease
dc.subjectProto-Oncogene Proteins c-myc
dc.subjectRepressor Proteins
dc.subjectApoptosis
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectProtein Binding
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAlleles
dc.subjectQuantitative Trait Loci
dc.subjectInterferon Regulatory Factors
dc.subjectEnhancer Elements, Genetic
dc.subjectPromoter Regions, Genetic
dc.titleMultiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with CDCA7L expression.
dc.typeJournal Article
dcterms.dateAccepted2016-10-19
rioxxterms.versionofrecord10.1038/ncomms13656
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-11-24
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.notesNo embargo
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/Cancer Genomics
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.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/Cancer Genomics
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-statusPublished
pubs.volume7en_US
pubs.embargo.termsNo embargo
icr.researchteamCancer Genomicsen_US
icr.researchteamMolecular & Population Geneticsen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorLi, Nien
dc.contributor.icrauthorKaiser, Martinen
dc.contributor.icrauthorHoulston, Richarden
dc.contributor.icrauthorJohnson, Daviden
dc.contributor.icrauthorStudd, Jamesen


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