Figure 5. Kras^ex3op allele confers dose-specific resistance to urethane.

(A) Strategy to generate 129 background Kras^ex3op/ex3op, Kras^ex3op/nat, and Kras^nat/nat cohorts for treatment with urethane. (B and C) Reduction of tumor burden (mean ± SEM) in mice carrying the Kras^ex3op allele (B) 4 months (n ≥5, **P < 0.01) and (C) 6 months (n ≥9, ****P < 0.0001) after urethane administration. (D) Ion Torrent sequencing of Kras cDNAs from the indicated number (n) of tumors arising in the indicated urethane-treated mice reveals fewer mutations in the Kras^ex3op allele. Pie charts are sized to reflect differences in overall tumor multiplicity for each genotype. P values were calculated by 1-way ANOVA with Bonferroni’s multiple comparisons test.