It is tempting to speculate that, since FBXW7 loss of function is a driver alongside NOTCH1 gain-of-function mutations in T-ALL and CLL, selection of NOTCH1 loss-of-function mutations in the normal epithelia would be accompanied by selection of gain-of-function FBXW7 mutations. The gene discussed is NOTCH1; the disease is B-cell chronic lymphocytic leukemia.