We speculate that the residual tumorigenic potential may reflect the oncogenic activities from mutations in other tumor suppressor genes (e.g., PTEN, TP53, CDKN2A) and oncogenes (e.g., TERT promoter) in 786-O that might cooperate with VHL mutation in initial ccRCC development in patients. The gene discussed is VHL; the disease is nonpapillary renal cell carcinoma.