SMAD4 and neoplasm: Also, the LOH of chromosome 18q causes the deletion of tumor suppresser genes such as DCC, SMAD2, and SMAD4, the mutation of which leads to the upregulation of enzymes involved in the glycolysis pathway, such as PKM2, HK2, and GLUT1 [29], as an early event in premalignant colonic mucosa and CRC progression [41].