VHL and nonpapillary renal cell carcinoma: To establish the strength of the technique we used the VHL-defective ccRCC cell line SKRC746 and its VHL-complemented variant SKRC7-VHLHA (expressing functional VHL with a haemagglutinin-tag) as a prototypical isogenic cell line pair with different metabolic characteristics: the lack of VHL in SKRC7 results in constitutive stabilization of HIF-1α and HIF-2α and a pseudohypoxic response39, 46, 47.