dc.contributor.author | Vijayakrishnan, J | |
dc.contributor.author | Qian, M | |
dc.contributor.author | Studd, JB | |
dc.contributor.author | Yang, W | |
dc.contributor.author | Kinnersley, B | |
dc.contributor.author | Law, PJ | |
dc.contributor.author | Broderick, P | |
dc.contributor.author | Raetz, EA | |
dc.contributor.author | Allan, J | |
dc.contributor.author | Pui, C-H | |
dc.contributor.author | Vora, A | |
dc.contributor.author | Evans, WE | |
dc.contributor.author | Moorman, A | |
dc.contributor.author | Yeoh, A | |
dc.contributor.author | Yang, W | |
dc.contributor.author | Li, C | |
dc.contributor.author | Bartram, CR | |
dc.contributor.author | Mullighan, CG | |
dc.contributor.author | Zimmerman, M | |
dc.contributor.author | Hunger, SP | |
dc.contributor.author | Schrappe, M | |
dc.contributor.author | Relling, MV | |
dc.contributor.author | Stanulla, M | |
dc.contributor.author | Loh, ML | |
dc.contributor.author | Houlston, RS | |
dc.contributor.author | Yang, JJ | |
dc.date.accessioned | 2020-05-28T11:29:06Z | |
dc.date.issued | 2019-11-25 | |
dc.identifier.citation | Nature communications, 2019, 10 (1), pp. 5348 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3651 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-019-13069-6 | |
dc.description.abstract | There is increasing evidence for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children. To identify new risk variants for B-cell ALL (B-ALL) we conducted a meta-analysis with four GWAS (genome-wide association studies), totalling 5321 cases and 16,666 controls of European descent. We herein describe novel risk loci for B-ALL at 9q21.31 (rs76925697, P = 2.11 × 10-8), for high-hyperdiploid ALL at 5q31.1 (rs886285, P = 1.56 × 10-8) and 6p21.31 (rs210143 in BAK1, P = 2.21 × 10-8), and ETV6-RUNX1 ALL at 17q21.32 (rs10853104 in IGF2BP1, P = 1.82 × 10-8). Particularly notable are the pleiotropic effects of the BAK1 variant on multiple haematological malignancies and specific effects of IGF2BP1 on ETV6-RUNX1 ALL evidenced by both germline and somatic genomic analyses. Integration of GWAS signals with transcriptomic/epigenomic profiling and 3D chromatin interaction data for these leukaemia risk loci suggests deregulation of B-cell development and the cell cycle as central mechanisms governing genetic susceptibility to ALL. | |
dc.format | Electronic | |
dc.format.extent | 5348 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | RNA-Binding Proteins | |
dc.subject | Oncogene Proteins, Fusion | |
dc.subject | Risk Factors | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Child | |
dc.subject | Core Binding Factor Alpha 2 Subunit | |
dc.subject | bcl-2 Homologous Antagonist-Killer Protein | |
dc.subject | Precursor B-Cell Lymphoblastic Leukemia-Lymphoma | |
dc.subject | Genome-Wide Association Study | |
dc.subject | Epigenomics | |
dc.subject | Transcriptome | |
dc.title | Identification of four novel associations for B-cell acute lymphoblastic leukaemia risk. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-10-17 | |
rioxxterms.versionofrecord | 10.1038/s41467-019-13069-6 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-11-25 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
pubs.notes | Not 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/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-status | Published | |
pubs.volume | 10 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Genomics | |
dc.contributor.icrauthor | Vijayakrishnan, Jayaram | |
dc.contributor.icrauthor | Studd, James | |
dc.contributor.icrauthor | Kinnersley, Benjamin | |
dc.contributor.icrauthor | Law, Philip | |
dc.contributor.icrauthor | Broderick, Peter | |
dc.contributor.icrauthor | Houlston, Richard | |