Thus, molecular studies in CCRCC have defined the dysregulation of the VHL gene as an almost universal initial, founding event, followed by different types of additional genetic events involving PBRM1, KDM5C, SETD2, or BAP1 that differentially dictate disease progression and aggressiveness [178,179]. The gene discussed is KDM5C; the disease is nonpapillary renal cell carcinoma.