PBRM1 and nonpapillary renal cell carcinoma: 3p LOH and silencing of the remaining VHL allele, either by somatic mutation or promoter hypermethylation, lead to complete inactivation of VHL. Besides VHL, three more ccRCC driver genes, PBRM1, BAP1 and SETD2, are also located between 3p25 and 3p21, the common site of 3p LOH in ccRCCs12, 14.