SMAD4 and colorectal carcinoma: In a genome-wide analysis by the Cancer Genome Atlas Network in 2012, mutations with high frequency in CRC primary foci included WNT (APC, CTNNB1, SOX9, TCF7L2, DKK, AXIN2, FBXW7, ARID1A, and FAM123B), PI3K, RAS-MAPK (IGF2, IRS2, PIK3R1, PIK3CA, PTEN, KRAS, NRAS, BRAF, ERBB2, and ERBB3), transforming growth factor-β (TGF-β) (TGFBR1, TGFBR2, ACVR2A, ACVR1B, Smad2, SMAD3, and Smad4), and p53 (53 and ATM) [26].