VHL and nonpapillary renal cell carcinoma: Among both primary and metastatic ccRCC tumors, the most frequently altered genes included VHL, PBRM1, SETD2, BAP1, and KDM5C, with KDM5C mutations less commonly observed among the highest FOLH1 expression quartile (FOLH1 Q4: 6% versus 12–18%, p < 0.05) (Figure 3A).