SMAD4 and cancer: This cancer harbors the “big 4” driver mutations, i.e., substitutions or alterations in the KRAS proto-oncogene, GTPase (KRAS), TP53, cyclin-dependent kinase inhibitor 2A, and mothers against decapentaplegic homolog 4 (https://cancer.sanger.ac.uk/census; https://portal.gdc.cancer.gov).