In support of the ‘bottom-up’ model, one efficient route is where intestinal stem cells (ISCs) are transformed via Apc loss or stable expression of β-catenin and very rapidly form adenomas.3, 4, 5 At the same time, experimental evidence also supports the ‘top-down’ model of intestinal tumourigenesis, where non-ISCs are transformed and serve as cells of origin. Here, APC is linked to adenoma.