The transcriptional program in colorectal cancer cells is profoundly affected by genetic alterations in cellular signaling systems such as WNT/APC/β-catenin, epidermal growth factor receptor (EGFR)/RAS/MEK/ERK and DPC4/SMAD4/TGF-β pathways as well as in transcriptional regulators such as TP53 [20]. The gene discussed is SMAD4; the disease is colorectal cancer.