SMAD4 and colorectal carcinoma: The characterization of genomic alterations in CRC by TCGA have already revealed that APC, TP53, SMAD4, PIK3CA, and KRAS mutations were most prevalent (69), in which APC, TP53, and KRAS/NARS/BRAF mutations have been found to be highly predictive for outcomes in clinical practice (41, 70).