Development of PC neoplasm and lymphoma phenotype in aged KO mice. (A) Kaplan-Meier plots illustrating lymphoma-free survival for aging cohorts of WT (n = 35) and KO (n = 36) mice. P value was calculated by using the log-rank test. (B) Representative images of spleens (Sp), LNs, and liver from an age-matched WT healthy control mouse and 1 each with the indicated lymphoma phenotype from KO mice. Note enlarged spleen and LNs, and tumor nodules in the liver (white arrowheads) of KO mice. (C) Comparison of spleen/body weight ratios between age-matched WT healthy controls (blue) and KO (red) mice with the indicated lymphoma phenotypes. P values were calculated by using the unpaired Student t test. (D) Clonality evaluated by Southern blot analysis of the IgH gene in DNA isolated from LNs, spleen (Sp), main tumor mass (T), or liver (Li) from KO mice with the indicated phenotypes. The nonrearranged germ line (GL) band (dashed gray line) and 1 to 3 clonally rearranged bands per mouse were identified (arrowheads). (E) Histologic and IHC stains of indicated markers on serial consecutive LN sections from representative KO mice with the indicated lymphoma phenotype. Hematoxylin-and-eosin (H&E) stain. Scale bars: yellow, 100 µm; white, 20 µm. (F) Number of SNVs and indels in the PC neoplasm and DLBCL from KO mice determined using WES. Colors represent mutation types. (G) Location of mutations in exemplary affected proteins in mouse DLBCL and PC neoplasm as well as human non-Hodgkin lymphomas (NHL). Colors represent mutation types as in panel F.