The development of CRC is underpinned by the accumulation of loss- or gain-of-function mutations in key driver genes (e.g. APC, KRAS, TP53 and SMAD4), which collectively disrupt signalling pathways that impinge on the proliferation and survival of differentiated and stem/progenitor cells within the intestinal epithelium8. Here, SMAD4 is linked to colorectal carcinoma.