Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
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- dc.contributor.author Puente, Xosé S.
- dc.contributor.author Escaramís, Geòrgia
- dc.contributor.author Bassaganyas Bars, Laia, 1985-
- dc.contributor.author Tubio, José M. C.
- dc.contributor.author Tornador Antolin, Cristian, 1979-
- dc.contributor.author Himmelbauer, Heinz
- dc.contributor.author Castillo Andreo, Esther
- dc.contributor.author Dohm, Juliane C.
- dc.contributor.author Guigó Serra, Roderic
- dc.contributor.author Estivill, Xavier, 1955-
- dc.contributor.author Campo, Elias
- dc.date.accessioned 2019-04-08T11:30:00Z
- dc.date.available 2019-04-08T11:30:00Z
- dc.date.issued 2011
- dc.description.abstract Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer.
- dc.format.mimetype application/pdf
- dc.identifier.citation Puente XS, Pinyol M, Quesada V, Conde L, Ordóñez GR, Villamor N et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature. 2011 Jun 5;475(7354):101-5. DOI: 10.1038/nature10113
- dc.identifier.doi http://dx.doi.org/10.1038/nature10113
- dc.identifier.issn 0028-0836
- dc.identifier.uri http://hdl.handle.net/10230/37065
- dc.language.iso eng
- dc.publisher Nature Research
- dc.relation.ispartof Nature. 2011 Jun 5;475(7354):101-5
- dc.rights © 2011 Macmillan Publishers Limited. All rights reserved. This paper is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence, and is freely available to all readers at www.nature.com/nature
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/
- dc.subject.other Genoma humà
- dc.subject.other Leucèmia limfocítica crònica
- dc.subject.other Mutagènesi
- dc.title Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion