PIK3CA and lung adenocarcinoma in situ: MAP2K1 mutation has been identified among subsets of smoking-associated lung carcinomas (mutually exclusive from EGFR, BRAF, KRAS, and NRAS mutations) [59, 60], lung adenocarcinoma in situ and early invasive disease [61], and KRAS/NRAS/BRAF/PIK3CA wild-type (“quadruple-wild-type”) colorectal carcinomas [62].