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dc.contributor.authorSpeedy, HEen_US
dc.contributor.authorBeekman, Ren_US
dc.contributor.authorChapaprieta, Ven_US
dc.contributor.authorOrlando, Gen_US
dc.contributor.authorLaw, PJen_US
dc.contributor.authorMartín-García, Den_US
dc.contributor.authorGutiérrez-Abril, Jen_US
dc.contributor.authorCatovsky, Den_US
dc.contributor.authorBeà, Sen_US
dc.contributor.authorClot, Gen_US
dc.contributor.authorPuiggròs, Men_US
dc.contributor.authorTorrents, Den_US
dc.contributor.authorPuente, XSen_US
dc.contributor.authorAllan, JMen_US
dc.contributor.authorLópez-Otín, Cen_US
dc.contributor.authorCampo, Een_US
dc.contributor.authorHoulston, RSen_US
dc.contributor.authorMartín-Subero, JIen_US
dc.date.accessioned2020-06-03T10:26:02Z
dc.date.issued2019-08-09en_US
dc.identifier.citationNature communications, 2019, 10 (1), pp. 3615 - ?en_US
dc.identifier.issn2041-1723en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3682
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/s41467-019-11582-2en_US
dc.description.abstractGenome-wide association studies have provided evidence for inherited genetic predisposition to chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms underlying CLL risk we analyze chromatin accessibility, active regulatory elements marked by H3K27ac, and DNA methylation at 42 risk loci in up to 486 primary CLLs. We identify that risk loci are significantly enriched for active chromatin in CLL with evidence of being CLL-specific or differentially regulated in normal B-cell development. We then use in situ promoter capture Hi-C, in conjunction with gene expression data to reveal likely target genes of the risk loci. Candidate target genes are enriched for pathways related to B-cell development such as MYC and BCL2 signalling. At 14 loci the analysis highlights 63 variants as the probable functional basis of CLL risk. By integrating genetic and epigenetic information our analysis reveals novel insights into the relationship between inherited predisposition and the regulatory chromatin landscape of CLL.en_US
dc.formatElectronicen_US
dc.format.extent3615 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectB-Lymphocytesen_US
dc.subjectChromatinen_US
dc.subjectHumansen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectProto-Oncogene Proteins c-mycen_US
dc.subjectProto-Oncogene Proteins c-bcl-2en_US
dc.subjectTranscription Factorsen_US
dc.subjectDNA Methylationen_US
dc.subjectEpigenesis, Geneticen_US
dc.subjectGene Expression Regulation, Leukemicen_US
dc.subjectBase Sequenceen_US
dc.subjectGenotypeen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectLeukemia, Lymphocytic, Chronic, B-Cellen_US
dc.subjectPromoter Regions, Geneticen_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectEpigenomicsen_US
dc.titleInsight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-07-23en_US
rioxxterms.versionofrecord10.1038/s41467-019-11582-2en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2019-08-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNature communicationsen_US
pubs.issue1en_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/Cancer Genomics
pubs.publication-statusPublisheden_US
pubs.volume10en_US
pubs.embargo.termsNot knownen_US
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorLaw, Philipen_US
dc.contributor.icrauthorHoulston, Richarden_US


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