PIK3CA and thyroid cancer, nonmedullary, 2: The mutated genes that affect these pathways encode cell-membrane receptors with tyrosine kinases activity such as RET and NTRK1 and intracellular signal transducers, among which BRAF and RAS. On the other hand, PI3K/AKT pathway, which is mainly involved in FTC initiation, is driven by activating mutations in RAS, PIK3CA, and AKT1 as well as by inactivation of PTEN. Mutations of TP53 and Wnt/βcatenin are indeed involved in the progression from PTC to PDTC and ATC.