Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

This paper is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence.-- et al.

Detalles Bibliográficos
Autores: González, Marcos, Hernández, Jesús M., Álava, Enrique de, San Miguel, Jesús F., Klatt, Peter
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/63719
Acceso en línea:http://hdl.handle.net/10261/63719
Access Level:acceso abierto
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spelling Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemiaGonzález, MarcosHernández, Jesús M.Álava, Enrique deSan Miguel, Jesús F.Klatt, PeterThis paper is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence.-- et al.Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution(1,2). 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(3,4). 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.This work was funded by the Spanish Ministry of Science and Innovation (MICINN) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII. C.L.-O. is an Investigator of the Botin Foundation and D.T., of the ICREA program. We thank E. Santos for his support of this project, A. Carracedo and J. Benítez for genotyping studies, C. Fortuny for the supply of samples and N. Villahoz and M. C. Muro for their work in the coordination of the CLL-ICGC Consortium.Peer ReviewedNature Publishing Group2013201320112013info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/63719reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglésinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/637192026-05-22T06:33:51Z
dc.title.none.fl_str_mv Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
title Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
spellingShingle Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
González, Marcos
title_short Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
title_full Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
title_fullStr Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
title_full_unstemmed Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
title_sort Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
dc.creator.none.fl_str_mv González, Marcos
Hernández, Jesús M.
Álava, Enrique de
San Miguel, Jesús F.
Klatt, Peter
author González, Marcos
author_facet González, Marcos
Hernández, Jesús M.
Álava, Enrique de
San Miguel, Jesús F.
Klatt, Peter
author_role author
author2 Hernández, Jesús M.
Álava, Enrique de
San Miguel, Jesús F.
Klatt, Peter
author2_role author
author
author
author
description This paper is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence.-- et al.
publishDate 2011
dc.date.none.fl_str_mv 2011
2013
2013
2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/63719
url http://hdl.handle.net/10261/63719
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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