Non-coding recurrent mutations in chronic lymphocytic leukaemia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-10

AUTHORS

Xose S. Puente, Silvia Beà, Rafael Valdés-Mas, Neus Villamor, Jesús Gutiérrez-Abril, José I. Martín-Subero, Marta Munar, Carlota Rubio-Pérez, Pedro Jares, Marta Aymerich, Tycho Baumann, Renée Beekman, Laura Belver, Anna Carrio, Giancarlo Castellano, Guillem Clot, Enrique Colado, Dolors Colomer, Dolors Costa, Julio Delgado, Anna Enjuanes, Xavier Estivill, Adolfo A. Ferrando, Josep L. Gelpí, Blanca González, Santiago González, Marcos González, Marta Gut, Jesús M. Hernández-Rivas, Mónica López-Guerra, David Martín-García, Alba Navarro, Pilar Nicolás, Modesto Orozco, Ángel R. Payer, Magda Pinyol, David G. Pisano, Diana A. Puente, Ana C. Queirós, Víctor Quesada, Carlos M. Romeo-Casabona, Cristina Royo, Romina Royo, María Rozman, Nuria Russiñol, Itziar Salaverría, Kostas Stamatopoulos, Hendrik G. Stunnenberg, David Tamborero, María J. Terol, Alfonso Valencia, Nuria López-Bigas, David Torrents, Ivo Gut, Armando López-Guillermo, Carlos López-Otín, Elías Campo

ABSTRACT

Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3' region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to ≥4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia. More... »

PAGES

519

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature14666

    DOI

    http://dx.doi.org/10.1038/nature14666

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1017405010

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26200345


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