Mutation spectra and significantly mutated genes. (A) The somatic point mutation spectrum observed genome-wide in each of the 40 cases. Overall, mutations affecting TA base pairs were more common than CG pairs, with TA>CG transitions the most common mutation observed on average. Some of the outliers, such as RG043, RG014, and RG111, harbored mutations in genes involved in DNA repair (supplemental Table 1; “Discussion”). (B) Mutated genes with significant evidence for positive selection (false discovery rate = 0.08) are ordered on the x-axis based on selective pressure estimate. The y-axis shows the adjusted P value such that highly significant genes, typically because of a larger number of observed mutations, lie toward the upper right. The size of the circles is proportional to the number of cases in the patient cohort in which a nonsilent or splice site SNV was identified. Significant genes identified in the larger patient cohort in our previous RNA-seq study are purple, and those identified in separate studies^3-5  are blue. The remaining 41 genes shown in pink have not, to our knowledge, been identified by others as significant targets of point mutation in DLBCL. Genes denoted with crosshairs indicate those with secondary support for mutations from other studies or the 13 DLBCL cell lines sequenced here (see supplemental Table 2 for details and references). Genes affected by splice site mutations included the known tumor suppressor genes MLL2, RB1, CREBBP, and TP53, as well as others with signatures indicative of inactivation, including DNAH5 and SGK1.