SMAD4 and neoplasm: Of the 24 significantly mutated genes identified in the S4low group, 12 were oncogenes associated with tumor progression or tumor suppressor genes (PIK3CA, KRAS, RHOA, CDH1, CTNNB1, ITGAV, SMAD4, TP53, CDKN2A, APC, PTEN, and PIK3R1; Table S1c).