VHL and nonpapillary renal cell carcinoma: In a study conducted by Brauch et al. on 227 sporadic ccRCC tumors analyzed for VHL-altering events, it was found that the combined rate of VHL mutation and promoter hypermethylation was 45%.75 The study further identified that the presence of VHL mutation or hypermutation events was significantly associated with poor prognostic markers, notably for the pT3 tumor stage.