PIK3CA and carcinoma: The PIK3CA p.R38H (Tumor 2) and p.R88Q (Tumor 1) variants both affect the adaptor-binding domain of the encoded protein; in vitro studies show gain of function through Akt signaling for both variants [19; 20], which are recurrent in carcinomas including squamous cell carcinoma and colonic adenocarcinoma [14, 21].