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dc.contributor.authorLin, W-Y
dc.contributor.authorFordham, SE
dc.contributor.authorSunter, N
dc.contributor.authorElstob, C
dc.contributor.authorRahman, T
dc.contributor.authorWillmore, E
dc.contributor.authorShepherd, C
dc.contributor.authorStrathdee, G
dc.contributor.authorMainou-Fowler, T
dc.contributor.authorPiddock, R
dc.contributor.authorMearns, H
dc.contributor.authorBarrow, T
dc.contributor.authorHoulston, RS
dc.contributor.authorMarr, H
dc.contributor.authorWallis, J
dc.contributor.authorSummerfield, G
dc.contributor.authorMarshall, S
dc.contributor.authorPettitt, A
dc.contributor.authorPepper, C
dc.contributor.authorFegan, C
dc.contributor.authorForconi, F
dc.contributor.authorDyer, MJS
dc.contributor.authorJayne, S
dc.contributor.authorSellors, A
dc.contributor.authorSchuh, A
dc.contributor.authorRobbe, P
dc.contributor.authorOscier, D
dc.contributor.authorBailey, J
dc.contributor.authorRais, S
dc.contributor.authorBentley, A
dc.contributor.authorCawkwell, L
dc.contributor.authorEvans, P
dc.contributor.authorHillmen, P
dc.contributor.authorPratt, G
dc.contributor.authorAllsup, DJ
dc.contributor.authorAllan, JM
dc.date.accessioned2021-03-01T09:53:37Z
dc.date.available2021-03-01T09:53:37Z
dc.date.issued2021-01-28
dc.identifier.citationNature communications, 2021, 12 (1), pp. 665 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4365
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-020-20822-9
dc.description.abstractPrognostication in patients with chronic lymphocytic leukemia (CLL) is challenging due to heterogeneity in clinical course. We hypothesize that constitutional genetic variation affects disease progression and could aid prognostication. Pooling data from seven studies incorporating 842 cases identifies two genomic locations associated with time from diagnosis to treatment, including 10q26.13 (rs736456, hazard ratio (HR) = 1.78, 95% confidence interval (CI) = 1.47-2.15; P = 2.71 × 10 -9 ) and 6p (rs3778076, HR = 1.99, 95% CI = 1.55-2.55; P = 5.08 × 10 -8 ), which are particularly powerful prognostic markers in patients with early stage CLL otherwise characterized by low-risk features. Expression quantitative trait loci analysis identifies putative functional genes implicated in modulating B-cell receptor or innate immune responses, key pathways in CLL pathogenesis. In this work we identify rs736456 and rs3778076 as prognostic in CLL, demonstrating that disease progression is determined by constitutional genetic variation as well as known somatic drivers.
dc.formatElectronic
dc.format.extent665 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleGenome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia.
dc.typeJournal Article
dcterms.dateAccepted2020-12-16
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-020-20822-9
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2021-01-28
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
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.volume12
pubs.embargo.termsNo embargo
icr.researchteamCancer Genomics
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorHoulston, Richarden


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