Decades of research analyzing the genetic basis of CRC has resulted in the identification of several important driver genes including APC, KRAS, SMAD4, and TP53. In addition, recent large scale genomic analyses, such as The Cancer Genome Atlas (TCGA), have identified numerous additional recurrent somatic mutations, focal copy number alterations and gene expression changes3,4. Here, SMAD4 is linked to colorectal carcinoma.