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.