We subsequently learnt that the 786-pRC cell line we employed also contains a p53 mutation (personal communication from WG Kaelin to R Craven), although we do not believe this to be implicated either, since p53 mutations are rarely seen in RCC.3 The underlying biology leading to such dysregulation, and whether common or divergent mechanisms are responsible, remains uncertain, but its consistency across more than one type of RCC suggests that it is a key and potentially early event. This evidence concerns the gene TP53 and renal cell carcinoma.