BRAF and differentiated thyroid carcinoma: Although ATC can arise de novo, approximately 20% of afflicted patients have a history of differentiated thyroid cancer, and 20% to 30% have a coexisting differentiated thyroid tumor, which has led investigators to believe that ATC represents the final step of a multistep process of dedifferentiation, with activating driver mutations in BRAF and RAS genes in the early phases and of secondary oncogenic mutations of TP53, TERT promoter, EIF1 AX, and PIK3 A genes in later events [141, 142].