Yet, in VHL-single hit cells we also observed overexpression of genes encoding cytosolic ACO1 and IDH1 - critical components of reductive glutamine metabolism - again suggesting that these cells, in addition to effective forward progression of the TCA cycle, have also activated an oncogenic metabolic shift that is seen in RCC, including a partial reversal of the TCA cycle. This evidence concerns the gene VHL and renal cell carcinoma.