PIK3CA structure. Schematic diagram of Pik3ca protein illustrating functional domains and mutations (grouped by domain) reported to date [22, 30, 32, 33, 40, 41]. Codons with frequent missense mutations reported ('hotspots') are denoted by asterisks. Location of experimentally found mutations in this study are denoted in boldface. p85, PI3K p85 regulatory subunit binding domain; RBD, Ras binding domain; C2, calcium-dependent phospholipid-binding domain; Helical, PI3K helical domain; Kinase, PI3/4-kinase domain.