PIK3CA and head and neck squamous cell carcinoma: Furthermore, the same study suggested that APOEC-mediated mutagenesis significantly contributes to helical domain E545K and E542K gain of function mutations in PIK3CA, one of the most frequently altered genes in HNSCC (32 out of 58 PIK3CA mutations in the TCGA cohort are E545K/E542K mutations; [19, 21, 144, 145]).