CYT-high colon cancers had a significant association (p < 0.05) with mutations in ACVR1B, CIRH1A, SOX9, FAM123B, BRAF, SMAD4, CASP8, RIMS1, JPH3 and RNF43. On the other hand, CYT-low colon tumors were associated with missense, nonsense or splice-site mutations in APC, TGIF1, TP53 and SMAD2. Furthermore, FBXW7, KRAS, PIK3CA, NXT1, B2M and PCBP1 had equal mutation rates among CYT-high and -low colon cancers (Fig. 3e). Here, SMAD4 is linked to malignant colon neoplasm.