Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia

Víctor Quesada, Laura Conde, Neus Villamor, Gonzalo R. Ordóñez, Pedro Jares, Laia Bassaganyas, Andrew J. Ramsay, Sílvia Beà, Magda Pinyol, Alejandra Martínez-Trillos, Mónica López-Guerra, Dolors Colomer, Alba Navarro, Tycho Baumann, Marta Aymerich, María Rozman, Julio Delgado, Eva Giné, Jesús M. Hernández, Marcos González-DíazDiana A. Puente, Gloria Velasco, José M.P. Freije, José M.C. Tubío, Romina Royo, Josep L. Gelpí, Modesto Orozco, David G. Pisano, Jorge Zamora, Miguel Vázquez, Alfonso Valencia, Heinz Himmelbauer, Mónica Bayés, Simon Heath, Marta Gut, Ivo Gut, Xavier Estivill, Armando López-Guillermo, Xose S. Puente, Elías Campo, Carlos López-Otín

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Here we perform whole-exome sequencing of samples from 105 individuals with chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries. We found 1,246 somatic mutations potentially affecting gene function and identified 78 genes with predicted functional alterations in more than one tumor sample. Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals. Further analysis in 279 individuals with CLL showed that SF3B1 mutations were associated with faster disease progression and poor overall survival. This work provides the first comprehensive catalog of somatic mutations in CLL with relevant clinical correlates and defines a large set of new genes that may drive the development of this common form of leukemia. The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies.

Original languageEnglish
Pages (from-to)47-52
Number of pages6
JournalNature Genetics
Issue number1
Publication statusPublished - 1 Jan 2012


ASJC Scopus subject areas

  • Genetics

Cite this

Quesada, V., Conde, L., Villamor, N., Ordóñez, G. R., Jares, P., Bassaganyas, L., Ramsay, A. J., Beà, S., Pinyol, M., Martínez-Trillos, A., López-Guerra, M., Colomer, D., Navarro, A., Baumann, T., Aymerich, M., Rozman, M., Delgado, J., Giné, E., Hernández, J. M., ... López-Otín, C. (2012). Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nature Genetics, 44(1), 47-52. https://doi.org/10.1038/ng.1032