Further studies have revealed that ccRCC is a heterogeneous cancer with disparate genetic and molecular alterations beyond VHL mutation, such as mutations in genes encoding chromatin remodeling proteins, like polybromo 1(PBRM1) [4] and SET domain containing 2 (SETD2) [5], both associated with high tumor stage and poor prognosis. This evidence concerns the gene VHL and nonpapillary renal cell carcinoma.