KEAP1 and neoplasm: Interestingly, the frequency of KEAP1 mutation remained relatively low until the disease reached stage IV LUAD (Supplementary information, Fig. S9c), suggesting that it is a late event in tumor evolution.23 Given that some tumor suppressor genes had low mutation frequencies, we analyzed a combination of all tumor suppressor genes and found a significant increase in mutation frequencies as the disease progressed to higher stages (Supplementary information, Fig. S9c).