Additional driver mutations involving histone-modifying enzymes (e.g., KDM5C and KDM6A), components of the PI3K/AKT/mTOR pathway (TSC1, TSC2, MTOR, PIK3CA, and PTEN), and TP53 further contribute to disease progression and reflect the molecular heterogeneity of ccRCC [17,18,19]. This evidence concerns the gene AKT1 and nonpapillary renal cell carcinoma.