dc.contributor.author | Li, N | |
dc.contributor.author | Johnson, DC | |
dc.contributor.author | Weinhold, N | |
dc.contributor.author | Studd, JB | |
dc.contributor.author | Orlando, G | |
dc.contributor.author | Mirabella, F | |
dc.contributor.author | Mitchell, JS | |
dc.contributor.author | Meissner, T | |
dc.contributor.author | Kaiser, M | |
dc.contributor.author | Goldschmidt, H | |
dc.contributor.author | Hemminki, K | |
dc.contributor.author | Morgan, GJ | |
dc.contributor.author | Houlston, RS | |
dc.date.accessioned | 2017-01-04T13:52:32Z | |
dc.date.issued | 2016-11-24 | |
dc.identifier.citation | Nature communications, 2016, 7 pp. 13656 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/362 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/ncomms13656 | |
dc.description.abstract | Genome-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 × 10-25), 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 × 10-36), 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.format | Electronic | |
dc.format.extent | 13656 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Multiple Myeloma | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Proto-Oncogene Proteins c-myc | |
dc.subject | Repressor Proteins | |
dc.subject | Apoptosis | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Protein Binding | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Alleles | |
dc.subject | Quantitative Trait Loci | |
dc.subject | Interferon Regulatory Factors | |
dc.subject | Enhancer Elements, Genetic | |
dc.subject | Promoter Regions, Genetic | |
dc.title | Multiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with CDCA7L expression. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-10-19 | |
rioxxterms.versionofrecord | 10.1038/ncomms13656 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-11-24 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.notes | No 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-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Cancer Genomics | |
icr.researchteam | Molecular & Population Genetics | |
icr.researchteam | Myeloma Group | |
dc.contributor.icrauthor | Li, Ni | |
dc.contributor.icrauthor | Studd, James | |
dc.contributor.icrauthor | Kaiser, Martin | |
dc.contributor.icrauthor | Houlston, Richard | |