Collectively, our results suggest that: (i) a subset of CRC is characterized by a genomic signature denoting concomitant deregulation of TP53 and APC, and (ii) the coexistence of TP53 and APC mutations predicts shorter PFS and OS only in the absence of mutations in other genes collocated in the WNT signaling, and that also intersect the p53 network at the protein level. This evidence concerns the gene APC and colorectal carcinoma.