VHL and nonpapillary renal cell carcinoma: Large-scale genomic projects have suggested that prevalence of germline and cancer-predisposing mutations were higher among patients with ccRCC compared with normal tissues, including VHL, PBRM1, SETD2, and BAP1, whereas how these mutations contribute to the pathogenesis and values as prognostic biomarkers in ccRCC are largely unknown (Peña-Llopis et al., 2012; Cancer Genome Atlas Research Network, 2013; Sato et al., 2013; Xu et al., 2016).