SMAD4 and adenoma: Thus, bi-allelic mutations in APC (adenomatous polyposis coli) lead to the formation of an early adenoma, which progresses to a late adenoma through activating KRAS mutations and loss of chromosome 18q, which leads to a loss of SMAD4. Finally, deletion of chromosome 17p leads to the loss of TP53, promoting the malignant transformation of late adenoma to a colorectal carcinoma [6], due to the dysregulation of Wnt/β-catenin, MAPK, PI3K, and TGF-β pathways.