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dc.contributor.authorCornish, AJ
dc.contributor.authorHoang, PH
dc.contributor.authorDobbins, SE
dc.contributor.authorLaw, PJ
dc.contributor.authorChubb, D
dc.contributor.authorOrlando, G
dc.contributor.authorHoulston, RS
dc.date.accessioned2019-01-08T12:29:04Z
dc.date.issued2019-01
dc.identifier.citationBlood advances, 2019, 3 (1), pp. 21 - 32
dc.identifier.issn2473-9529
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2998
dc.identifier.eissn2473-9537
dc.identifier.doi10.1182/bloodadvances.2018026419
dc.description.abstractThe identification of driver mutations is fundamental to understanding oncogenesis. Although genes frequently mutated in B-cell lymphoma have been identified, the search for driver mutations has largely focused on the coding genome. Here we report an analysis of the noncoding genome using whole-genome sequencing data from 117 patients with B-cell lymphoma. Using promoter capture Hi-C data in naive B cells, we define cis -regulatory elements, which represent an enriched subset of the noncoding genome in which to search for driver mutations. Regulatory regions were identified whose mutation significantly alters gene expression, including copy number variation at cis -regulatory elements targeting CD69 , IGLL5 , and MMP14 , and single nucleotide variants in a cis -regulatory element for TPRG1 We also show the commonality of pathways targeted by coding and noncoding mutations, exemplified by MMP14 , which regulates Notch signaling, a pathway important in lymphomagenesis and whose expression is associated with patient survival. This study provides an enhanced understanding of lymphomagenesis and describes the advantages of using chromosome conformation capture to decipher noncoding mutations relevant to cancer biology.
dc.formatPrint
dc.format.extent21 - 32
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectHumans
dc.subjectLymphoma, B-Cell
dc.subjectGenetic Predisposition to Disease
dc.subjectRNA, Untranslated
dc.subjectComputational Biology
dc.subjectGene Amplification
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectMutation
dc.subjectOpen Reading Frames
dc.subjectDatabases, Genetic
dc.subjectPromoter Regions, Genetic
dc.subjectGenetic Association Studies
dc.subjectDNA Copy Number Variations
dc.subjectWhole Genome Sequencing
dc.titleIdentification of recurrent noncoding mutations in B-cell lymphoma using capture Hi-C.
dc.typeJournal Article
dcterms.dateAccepted2018-11-24
rioxxterms.versionofrecord10.1182/bloodadvances.2018026419
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBlood advances
pubs.issue1
pubs.notesNot 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-statusPublished
pubs.volume3
pubs.embargo.termsNot known
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorCornish, Alexanderen
dc.contributor.icrauthorLaw, Philipen
dc.contributor.icrauthorHoulston, Richarden


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