VHL and nonpapillary renal cell carcinoma: We showed that the Vhl mutation is essential for the formation of ccRCC tumors in the Trp53/Rb1 mutant background [14], reproducing one of the hallmark pathological features of human ccRCC and further showing genetically that tumor formation in this model is strongly dependent on HIF-1α but only weakly affected by genetic ablation of HIF-2α [2].