KMT2D and lung cancer: Most of the commonly mutated genes in both mouse and human LUSCs have genetic and/or functional significance to lung cancer, such as Kmt2d (Mll2), Zeb2, Braf, Igf2r, Flt1, Atr, Muc4, Ncoa3 (Src3), and Ido1. KMT2D, the key enzyme governing histone modification, is a well-known driver gene with a high somatic mutation rate in LUSC tumors [14, 21].