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dc.contributor.authorHoang, PHen_US
dc.contributor.authorDobbins, SEen_US
dc.contributor.authorCornish, AJen_US
dc.contributor.authorChubb, Den_US
dc.contributor.authorLaw, PJen_US
dc.contributor.authorKaiser, Men_US
dc.contributor.authorHoulston, RSen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2019-02-20T08:11:28Z
dc.date.issued2018-11en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29654271en_US
dc.identifier10.1038/s41375-018-0103-3en_US
dc.identifier.citationLeukemia, 2018, 32 (11), pp. 2459 - 2470en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3069
dc.identifier.eissn1476-5551en_US
dc.identifier.doi10.1038/s41375-018-0103-3en_US
dc.description.abstractMultiple myeloma (MM) is a biologically heterogeneous malignancy, however, the mechanisms underlying this complexity are incompletely understood. We report an analysis of the whole-genome sequencing of 765 MM patients from CoMMpass. By employing promoter capture Hi-C in naïve B-cells, we identify cis-regulatory elements (CREs) that represent a highly enriched subset of the non-coding genome in which to search for driver mutations. We identify regulatory regions whose mutation significantly alters the expression of genes as candidate non-coding drivers, including copy number variation (CNV) at CREs of MYC and single-nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay between non-coding driver mutations with other driver mechanisms, and their respective roles in oncogenic pathways, we extended our analysis identifying coding drivers in 40 genes, including 11 novel candidates. We demonstrate the same pathways can be targeted by coding and non-coding mutations; exemplified by IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell differentiation. This study reveals new insights into the complex genetic alterations driving MM development and an enhanced understanding of oncogenic pathways.en_US
dc.format.extent2459 - 2470en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectCarcinogenesisen_US
dc.subjectCell Differentiationen_US
dc.subjectDNA Copy Number Variationsen_US
dc.subjectFemaleen_US
dc.subjectGenome, Humanen_US
dc.subjectHigh-Throughput Nucleotide Sequencingen_US
dc.subjectHumansen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectMultiple Myelomaen_US
dc.subjectMutationen_US
dc.subjectOncogenesen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectPromoter Regions, Geneticen_US
dc.subjectRegulatory Sequences, Nucleic Aciden_US
dc.subjectWhole Genome Sequencingen_US
dc.titleWhole-genome sequencing of multiple myeloma reveals oncogenic pathways are targeted somatically through multiple mechanisms.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-03-05en_US
rioxxterms.versionofrecord10.1038/s41375-018-0103-3en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2018-11en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfLeukemiaen_US
pubs.issue11en_US
pubs.notesNot knownen_US
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/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.publication-statusPublisheden_US
pubs.volume32en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMolecular & Population Geneticsen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorHoang, Phucen_US
dc.contributor.icrauthorCornish, Alexanderen_US
dc.contributor.icrauthorLaw, Philipen_US
dc.contributor.icrauthorKaiser, Martinen_US
dc.contributor.icrauthorHoulston, Richarden_US


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