Given the critical role of VHL inactivation in RCC, a marked response to demethylating therapy in cell lines with VHL hypermethylation might not appear unexpected, and indeed, preferential effects of 5-aza-2′-deoxycytidine treatment of VHL-methylated versus VHL-mutated but unmethylated cell lines were described in in vivo studies [20]. Here, VHL is linked to renal cell carcinoma.