Consistently, knockout of VHL, which would prevent degradation of EGLN1-hydroxylated HIF-1α, was also selectively essential in tRCC cells expressing high HIF1A (Extended Data Fig. 5c–f); VHL was dispensable both in the VHL-null ccRCC line 786-O and in the VHL-preserved ccRCC line Caki-177 (Extended Data Fig. 5g–h). This evidence concerns the gene HIF1A and nonpapillary renal cell carcinoma.