In a large Mayo cohort, the loss of H3K36me3 by IHC—a functional readout of SETD2—was linked to ~two-fold higher risks of RCC-specific death and progression and remained significant after adjustment in risk-stratified models; by contrast, SETD2 DNA/mRNA alone was less consistently prognostic [69,70,71]. The gene discussed is SETD2; the disease is renal cell carcinoma.