ccRCC is an extremely complex and heterogeneous neoplasia involves different aberrant genes included VHL, TP53, chromatin modifier genes (PBRM1, SETD2, BAP1, ARID1A, MLL3, KDM5C, SMARCB1), PI3K/AKT/mTOR pathway genes (MTOR, PTEN, PIK3CA), MET, Hippo pathway gene NF2, NRF2-ARE pathway gene NFE2L2, and cell cycle genes (CDKN2A) (89). This evidence concerns the gene PBRM1 and nonpapillary renal cell carcinoma.