We previously identified an acquired p53 mutation in a HIF2-independent subclone of the HIF2-dependent ccRCC cell line 786-O and Brugarolas and coworkers identified a p53 mutation, R273H, in a HIF2-independent ccRCC tumor in a ccRCC patient who had a mixed response to PT2385, suggesting that p53 mutations caused resistance (21, 28). Here, TP53 is linked to nonpapillary renal cell carcinoma.