Catalogue Of Somatic Mutations In Cancer (COSMIC)-annotated Eµ-TCL1^Akt-C–mutated genes define the model as a genetically intermediary form between CLL and DLBCL. (A) Schematic strategy to identify clonal VDJ rearrangements. Using the JH4 probe on EcoRI-digested genomic DNA results in a 6.2 kb germline configuration band in Southern blot analysis. Clonal VDJ rearrangements indicative of B-cell leukemia and lymphoma can be identified by clear bands other than 6.2 kb (upper panel). Southern blot analysis of Cd19⁺ MACS-purified B cells derived from indicated mice using the aforementioned strategy. (B) Flow diagram of WES experimental setup. (C) Distribution of variant allele frequencies (left panel) and mutations per case (right panel) between Cd19-Cre^Akt-C (n = 4), Eµ-TCL1 (n = 10), and Eµ-TCL1^Akt-C (n = 9) mice. (D) Waterfall plot of COSMIC-annotated mutations from Cd19-Cre^Akt-C (n = 4), Eµ-TCL1 (n = 10), and Eµ-TCL1^Akt-C (n = 9) mice. Mutations clustered according to normalized disease tendency scores of COSMIC CLL and DLBCL mutation data (pink = CLL-associated; yellow = DLBCL-associated; black = equal distribution). Mutations were annotated for occurrence in COSMIC Cancer Gene Census Tiers (blue = animal 1; red = animal 2), COSMIC Cancer Gene Census Hallmark classification (blue = across all cancers; red = leukemia/lymphoma-specific), observed to be mutated in RT. (E) Bar graph representing the mean normalized disease tendency scores per genotype (blue = Eµ-TCL1; red = Eµ-TCL1^Akt-C; green = M-B-Cd19). P values were generated via binomial testing, presuming equal chances of each gene being mutated in either CLL or DLBCL (0.5).