The clustering of mutations in hotspot exons (exons 14-16) of the SF3B1 gene suggests that these mutations have been subject to positive selection and serve as driving events in CLL pathology by giving rise to alternative splicing that affects cellular processes such as DNA damage response, telomere maintenance, and NOTCH signaling (29, 45–48). The gene discussed is SF3B1; the disease is B-cell chronic lymphocytic leukemia.