Colorectal adenoma-carcinoma sequence observed in most of the CRC cases in humans (CIN tumors, 84%) is associated with high frequency of DNA somatic copy number alterations (SCNA), with common mutations in APC, TP53, KRAS, SMAD4, and PIK3CA [7,10,18,19,20]. Here, SMAD4 is linked to colorectal carcinoma.