SMAD4 and carcinoma: The adenoma–carcinoma sequence of events in left-sided CRC carcinogenesis begins with the loss of the APC tumor suppressor gene followed by KRAS oncogene activation, p53 tumor suppressor gene inactivation, and other mutations in tumor suppressor (FBXW7, SMAD2, SMAD4, TCF7L2, FAM123B (WTX), ATM, and ARID1A) genes and oncogenes (PIK3CA, NRAS, CTNNB1, and SOX9) [27].