PBRM1 and nonpapillary renal cell carcinoma: Inactivating mutations (loss-of-heterozygosity) or epigenetic changes (mainly promoter hypermethylation) of the tumor suppressor gene VHL in particular are the main drivers of ccRCC, while loss of PBRM1, BAP1 or SETD2 is subordinate to VHL loss [12, 13].