Our analysis demonstrated the expected subclonal distribution of established gene mutations, such as TP53, ATM, SF3B1 and NOTCH1. Interestingly, all our somatically acquired SETD2 mutations exhibited a clonal cancer cell fraction, suggesting that these mutations may be early events in the evolution of CLL (Figures 2c and d and Supplementary Figures S5B and C), although further studies are required to confirm this observation. This evidence concerns the gene NOTCH1 and B-cell chronic lymphocytic leukemia.