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dc.contributor.authorRobbe, P
dc.contributor.authorRidout, KE
dc.contributor.authorVavoulis, DV
dc.contributor.authorDréau, H
dc.contributor.authorKinnersley, B
dc.contributor.authorDenny, N
dc.contributor.authorChubb, D
dc.contributor.authorAppleby, N
dc.contributor.authorCutts, A
dc.contributor.authorCornish, AJ
dc.contributor.authorLopez-Pascua, L
dc.contributor.authorClifford, R
dc.contributor.authorBurns, A
dc.contributor.authorStamatopoulos, B
dc.contributor.authorCabes, M
dc.contributor.authorAlsolami, R
dc.contributor.authorAntoniou, P
dc.contributor.authorOates, M
dc.contributor.authorCavalieri, D
dc.contributor.authorGenomics England Research Consortium,
dc.contributor.authorCLL pilot consortium,
dc.contributor.authorGibson, J
dc.contributor.authorPrabhu, AV
dc.contributor.authorSchwessinger, R
dc.contributor.authorJennings, D
dc.contributor.authorJames, T
dc.contributor.authorMaheswari, U
dc.contributor.authorDuran-Ferrer, M
dc.contributor.authorCarninci, P
dc.contributor.authorKnight, SJL
dc.contributor.authorMånsson, R
dc.contributor.authorHughes, J
dc.contributor.authorDavies, J
dc.contributor.authorRoss, M
dc.contributor.authorBentley, D
dc.contributor.authorStrefford, JC
dc.contributor.authorDevereux, S
dc.contributor.authorPettitt, AR
dc.contributor.authorHillmen, P
dc.contributor.authorCaulfield, MJ
dc.contributor.authorHoulston, RS
dc.contributor.authorMartín-Subero, JI
dc.contributor.authorSchuh, A
dc.coverage.spatialUnited States
dc.date.accessioned2023-01-04T14:14:40Z
dc.date.available2023-01-04T14:14:40Z
dc.date.issued2022-11-01
dc.identifier10.1038/s41588-022-01211-y
dc.identifier.citationNature Genetics, 2022, 54 (11), pp. 1675 - 1689
dc.identifier.issn1061-4036
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5643
dc.identifier.eissn1546-1718
dc.identifier.eissn1546-1718
dc.identifier.doi10.1038/s41588-022-01211-y
dc.description.abstractThe value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom's 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia.
dc.formatPrint-Electronic
dc.format.extent1675 - 1689
dc.languageeng
dc.language.isoeng
dc.publisherNATURE PORTFOLIO
dc.relation.ispartofNature Genetics
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectLeukemia, Lymphocytic, Chronic, B-Cell
dc.subjectWhole Genome Sequencing
dc.subjectMutation
dc.subjectGenomics
dc.subjectPrognosis
dc.titleWhole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features.
dc.typeJournal Article
dcterms.dateAccepted2022-09-16
dc.date.updated2023-01-04T14:13:56Z
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41588-022-01211-y
rioxxterms.licenseref.startdate2022-11-01
rioxxterms.typeJournal Article/Review
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/36333502
pubs.issue11
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.publisher-urlhttp://dx.doi.org/10.1038/s41588-022-01211-y
pubs.volume54
icr.researchteamCancer Genomics
dc.contributor.icrauthorKinnersley, Benjamin
dc.contributor.icrauthorCornish, Alexander
dc.contributor.icrauthorHoulston, Richard
icr.provenanceDeposited by Mr Arek Surman on 2023-01-04. Deposit type is initial. No. of files: 1. Files: Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features.pdf


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