VHL and nonpapillary renal cell carcinoma: Undoubtedly, the most frequent event in ccRCC is inactivation of the VHL gene as a result of allelic deletion, somatic mutation and/or promoter hypermethylation, which is well known in familial VHL tumor syndrome and nearly accounts for more than half of the entire cases, including sporadic renal cell carcinoma patients [4, 11–13].