Their malignant potential is explained by the accumulation of genetic alterations that may in turn depend upon the inactivation of the DNA repair gene MGMT. 28 The importance of these ‘fusion’ polyps as cancer precursors may be under-appreciated because critical rate-limiting changes governing malignant transition, particularly in association with loss of function of MLH1 of p53, occur rapidly and can rarely be ‘caught in the act’. The gene discussed is MLH1; the disease is cancer.