In agreement with this conclusion, numerous previous studies showed that deletion of Vhl in mouse renal epithelial cells in vivo10,57–62, resulting in abrogation of the many different tumour suppressor functions of pVHL2,7,63, was insufficient to cause tumour initiation either when both HIF-1α and HIF-2α were stabilised, or when the balance of HIF-1α and HIF-2α activities were genetically altered by co-deletion of Hif1a or Hif2a29. This evidence concerns the gene EPAS1 and neoplasm.