KRAS and cancer: As G12C is the most common KRAS oncogenic variant in LUAD (34, 35), we used a recently developed KRASG12C-driven LUAD mouse model (named KcP) (36) to test whether the additional loss of SETD2 (named KcP;Setd2) impacted cancer pathogenesis in vivo like it does in a G12D oncogenic mutant background (Figs. 1A-C).