In lung adenocarcinoma (LUAD), EGFR mutations were more prevalent in never-smokers than in smokers in both a small cohort (62% vs. 13%, p < 0.001) and a large cohort (65% vs. 41%, p < 0.001) [114,115] In large-cell carcinoma (LCC), no significant differences were observed between never-smokers and current/former smokers in the frequencies of EGFR, KRAS, ALK, or PIK3CA mutations (p = 0.45, 0.58, 1.00, and 0.62, respectively) [116]. Here, PIK3CA is linked to leukoencephalopathy with calcifications and cysts.