While it cannot be excluded that there might be differences between mice and humans, and the findings may be contextual to the Vhl/Trp53/Rb1 mutant background, this result seemingly contrasts with several independent lines of evidence from the study of human ccRCC tumours and ccRCC cell lines, which have demonstrated that HIF-2α possesses strong oncogenic activity and HIF-1α acts in the manner of a tumour suppressor to suppress aggressive tumour behaviour. Here, EPAS1 is linked to nonpapillary renal cell carcinoma.