Elevated HIF2α levels in VHL-mutant ccRCC are proposed to induce growth factor expression leading firstly to the AKT-mediated phosphorylation of HDM2, promoting its ability to degrade p53 (Roberts et al, 2009) or secondly to the suppression of formation of reactive oxygen species which reduce p53 activation (Bertout et al, 2009). This evidence concerns the gene VHL and nonpapillary renal cell carcinoma.