Mutually exclusive and co-occurring oncogene mutations in human cancer.

(A) Oncogene mutations were grouped together when they occurred within a given gene (e.g., 'KRAS' for all mutations in 'KRAS') or in the same functional domain of the encoded protein (e.g., 'PIK3CA_KD' for kinase domain mutations of PIK3CA). When a distinct phenotype was correlated with a mutation, the mutation was grouped separately (e.g., 'EGFR_T790M' for the T790M mutation of EGFR known to be correlated with resistance to EGFR inhibitors). Mutant samples (columns/black bars) are sorted by grouped oncogene mutations and by tumor type (color legend indicated). Red bars indicate co-occurring mutations. EGFR_ECD, extracellular domain mutations of EGFR; EGFR_KD, kinase domain mutations of EGFR; PIK3CA_KD, kinase domain mutation of PIK3CA; PIK3CA_HD, helical domain mutations of PIK3CA. (B) Incidence of BRAF mutations and co-occurring mutations in any RAS gene. (C) Incidence of co-occurring KRAS and PIK3CA mutations.