Fig 1: dDNMT specifically kills patient-derived VHL-deficient ccRCC in mice(A) Tumor growth curves of VHL-deficient UTSW-PDX206, UTSW-PDX258, UTSW-PDX490, and UTSW-PDX26 in mice treated with vehicle (Veh) or SGI1027 for 10 days.(B) Tumor growth curves of VHL-WT UTSW-PDX416 and UTSW-PDX143 in mice treated with vehicle or SGI1027 for 10 days.(C) Kaplan-Meier survival curve of UTSW-PDX490-bearing mice (n = 10 biological replicates).(D and E) Global m5C levels in UTSW-PDX206 (D) or UTSW-PDX258 (E) tumors harvested from mice after treatments by ELISA assay (n = 5 biological replicates).(F) Immunoblot analysis of DNMT1, DNMT3A, DNMT3B, TRAIL, DR4, DR5, procaspase-10, C-caspase-3, and C-caspase-7 proteins in UTSW-PDX258 tumors harvested from mice after treatments (n = 5 biological replicates).(G) Representative C-caspase-3 IHC in UTSW-PDX258 tumors. Scale bar, 100 μm.(H) Quantification of C-caspase-3-positive cells in (G) (n = 5 biological replicates).(I) Immunoblot analysis of DNMT1, DNMT3A, DNMT3B, TRAIL, DR4, DR5, C-caspase-3, and VHL proteins in UTSW-PDX416 tumors harvested from mice after treatments (n = 5 biological replicates).(J) Immunoblot analysis of DNMT1, DNMT3A, DNMT3B, and procaspase-10 proteins in UTSW-PDX206, UTSW-PDX258, and UTSW-PDX26 tumors (n = 4–5 biological replicates).Data represent mean ± SEM. p value was determined by two-way ANOVA with Tukey’s test (A), log rank test (C), and unpaired 2-tailed Student’s t test (D, E, and H). See also Figures S9 and S10; Table S3.