Whole-body SB transposon mutagenesis drives a diverse tumor spectrum in Trp53 wild type and mutant mice.

(A) Kaplan-Meier survival curves comparing experimental SB and non-SB control mouse cohorts (log-rank test, P < 0.0001). Wild type Trp53 cohorts with SB-Onc3 mobilized by a constitutively active Rosa26-SBase allele (Gray line, reported in [7]) do not differ significantly from SB-Onc3 mice mobilized by a conditionally activated Rosa26-LSL-SBase allele to the Rosa26-1lox-SBase allele by whole body Cre expression (log-rank test, P>0.05). Mice in all SB-Onc3 cohorts developed solid tumors, including cutaneous squamous cell carcinoma (cuSCC) and hepatocellular adenoma (HCA), but Trp53^+/− (red line) and Trp53^R172H/+ (blue line) mice had significantly decreased survival compared to the wild-type (WT) cohort (Green line, P<0.0001, log-rank). Non-SB control Trp53^R172H/+ mice (dashed black line) had significantly decreased survival compared to the WT cohort (solid black line, P<0.0001, log-rank). (B-C) Histology and tumor classification from sections of skin masses stained with hematoxylin and eosin. (B) Early-stage, non-invasive mass with cutaneous keratoacanthoma-like morphology (cuKA) in SB-Onc3|Trp53^+/+ mouse (20×). (C) Invasive mass with cuSCC displaying keratin pearl morphology in SB-Onc3|Trp53^KO/+ mouse (20×). (D) cuSCC keratin pearls in SB-Onc3|Trp53^+/+ mouse (100×). (E) cuSCC displaying lymphatic invasion in SB-Onc3|Trp53^R172H/+ mouse (200×). (F) cuSCC displaying muscle invasion in SB-Onc3|Trp53^+/+ mouse (200×).