Genetic complexity and convergent evolution in patient CLL33. (A) Convergent evolution was observed in 3 independent driver genes in 2 subclones. Subclone A had DDX3X (p.E196Dfs*30), SF3B1 (p.G742D), and del(11q22-23) genetic lesions. The emergent subclone B after relapse had independent mutations in DDX3X (p.D20Dfs*14) and SF3B1 (p.K700E), and del(11q22-q23). Additionally, del(17p13) and mutations in TP53 (p.D281N) and NOTCH1 (p.G2131Gfs*116) were identified in subclone B. (B) Different breakpoints for del(11q22-23) in subclones A and B were confirmed by aCGH (deleted regions in each time point are shown by dark gray and light gray blocks; breakpoints are indicated by broken lines). The genomic position of the breakpoints is shown at each time point. The deletion found at baseline was not found at relapse, as was confirmed using a custom FISH probe (RP11-159L10). Additionally, biallelic deletion affecting an already-defined copy number polymorphism in relapse samples but not in the baseline sample (marked with an asterisk) suggest that different chromosomes 11 (paternal versus maternal) were deleted in each subclone. The physical positions of probe RP11-159L10 and ATM are shown.