The initial generation of these combined transgenic mice (reviewed in (10, 21, 26, 27)), which included oncogenic Braf, Kras and Hras knock-ins, with the common cooperating alterations found in human genomic studies of advanced thyroid cancer (i.e. TERT promoter, TP53, PI3K pathway genes and EIF1AX), confirmed the ability of these cooperating mutations to promote tumor progression when combined with driver alterations. This evidence concerns the gene PIK3CA and neoplasm.