A gene signature derived from the loss of CDKN1A (p21) gene, obtained in HCT116 p21-/- colorectal cancer cells, is identified in a large cohort of primary colorectal (CRC) tumors and is associated with the Consensus Molecular Subtype (CMS) of colon cancer that has a worse relapse-free and overall survival, that is, CMS4 (also called mesenchymal subtype). Here, CDKN1A is linked to malignant colon neoplasm.