POU2F2 and nonpapillary renal cell carcinoma: Our data demonstrate that SETD2 and its downstream targets (SOX2, OCT2, and PRRX1) are key regulators of EMT and stemness, consistent with SETD2 loss promoting more aggressive ccRCC, and that these phenotypic effects are driven by both cell intrinsic and extrinsic mechanisms (Fig. 7E).