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dc.contributor.authorStudd, JB
dc.contributor.authorVijayakrishnan, J
dc.contributor.authorYang, M
dc.contributor.authorMigliorini, G
dc.contributor.authorPaulsson, K
dc.contributor.authorHoulston, RS
dc.date.accessioned2017-03-24T14:59:00Z
dc.date.issued2017-03-03
dc.identifier.citationNature communications, 2017, 8 pp. 14616 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/519
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/ncomms14616en_US
dc.description.abstractDespite high-hyperdiploid acute lymphoblastic leukaemia (HD-ALL) being the most common subgroup of paediatric ALL, its aetiology remains unknown. Genome-wide association studies have demonstrated association at 10q21.2. Here, we sought to determine how this region influences HD-ALL risk. We impute genotypes across the locus, finding the single nucleotide polymorphism rs7090445 highly associated with HD-ALL (P=1.54 × 10<sup>-38</sup>), and residing in a predicted enhancer element. We show this region physically interacts with the transcription start site of ARID5B, that alleles of rs7090445 have differential enhancer activity and influence RUNX3 binding. RUNX3 knock-down reduces ARID5B expression and rs7090445 enhancer activity. Individuals carrying the rs7090445-C risk allele also have reduced ARID5B expression. Finally, the rs7090445-C risk allele is preferentially retained in HD-ALL blasts consistent with inherited genetic variation contributing to arrest of normal lymphocyte development, facilitating leukaemic clonal expansion. These data provide evidence for a biological mechanism underlying hereditary risk of HD-ALL at 10q21.2.
dc.formatElectronic
dc.format.extent14616 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCell Line, Tumor
dc.subjectChromosomes, Human, Pair 10
dc.subjectHumans
dc.subjectGenetic Predisposition to Disease
dc.subjectDNA-Binding Proteins
dc.subjectTranscription Factors
dc.subjectSequence Analysis, RNA
dc.subjectEpigenesis, Genetic
dc.subjectGene Expression Regulation, Leukemic
dc.subjectDiploidy
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAlleles
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectCore Binding Factor Alpha 3 Subunit
dc.subjectPrecursor Cell Lymphoblastic Leukemia-Lymphoma
dc.subjectEnhancer Elements, Genetic
dc.subjectGenetic Variation
dc.subjectGenome-Wide Association Study
dc.subjectGenetic Loci
dc.titleGenetic and regulatory mechanism of susceptibility to high-hyperdiploid acute lymphoblastic leukaemia at 10p21.2.
dc.typeJournal Article
dcterms.dateAccepted2017-01-17
rioxxterms.versionofrecord10.1038/ncomms14616
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-03-03en_US
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
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-statusPublished
pubs.volume8en_US
pubs.embargo.termsNo embargo
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorVijayakrishnan, Jayaramen
dc.contributor.icrauthorHoulston, Richarden
dc.contributor.icrauthorStudd, Jamesen


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