| Literature DB >> 26200345 |
Xose S Puente1, Silvia Beà2, Rafael Valdés-Mas1, Neus Villamor3, Jesús Gutiérrez-Abril1, José I Martín-Subero4, Marta Munar5, Carlota Rubio-Pérez6, Pedro Jares7, Marta Aymerich3, Tycho Baumann8, Renée Beekman2, Laura Belver9, Anna Carrio3, Giancarlo Castellano2, Guillem Clot2, Enrique Colado10, Dolors Colomer3, Dolors Costa3, Julio Delgado8, Anna Enjuanes7, Xavier Estivill11, Adolfo A Ferrando9, Josep L Gelpí5, Blanca González3, Santiago González5, Marcos González12, Marta Gut13, Jesús M Hernández-Rivas12, Mónica López-Guerra3, David Martín-García2, Alba Navarro2, Pilar Nicolás14, Modesto Orozco5, Ángel R Payer10, Magda Pinyol7, David G Pisano15, Diana A Puente1, Ana C Queirós4, Víctor Quesada1, Carlos M Romeo-Casabona14, Cristina Royo2, Romina Royo5, María Rozman3, Nuria Russiñol2, Itziar Salaverría2, Kostas Stamatopoulos16, Hendrik G Stunnenberg17, David Tamborero6, María J Terol18, Alfonso Valencia15, Nuria López-Bigas6, David Torrents5, Ivo Gut13, Armando López-Guillermo8, Carlos López-Otín1, Elías Campo3.
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.Entities:
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Year: 2015 PMID： 26200345 DOI： 10.1038/nature14666
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962