In sharp contrast, around only 0.3% of the PTEN, SMAD4 or ARID1A mutations in tumours (mean: 0.25–0.39) can be described as passengers in this way (Fig. 2J), suggesting they are true cancer driver genes positively enriched in CRC beyond their level of selection in normal tissue. The gene discussed is SMAD4; the disease is colorectal carcinoma.