Intratumoral subpopulations are genetically divergent. Variant allele frequencies are compared between the CD20int (y-axis) and CD20hi (x-axis) intratumoral subpopulations. In most cases, only a minority of mutations are represented at approximately equal frequencies in each subpopulation (green dots). Many mutations comparably are enriched in either the CD20int (violet dots) or CD20hi (orange dots) subpopulation, or detected only in the CD20int (blue dots) or CD20hi (red dots) subpopulation. Mutations in selected genes of biologic interest are highlighted by letters A through J. Whereas CREBBP mutations (A) always appear in approximately equal frequencies in tumor cell subpopulations, MLL2 mutations are relatively enriched in 1 subpopulation in 3 of 4 tumors. Diagonal lines represent the threshold for 33% enrichment of variants in 1 subpopulation with reference to the alternate subpopulation (y = 1.33x and x = 1.33y), which allows 99% specificity for true subpopulation bias (supplemental Figure 1).