To this end, gene expression and immunohistochemical analyses comparing twelve month-old ccRCC tumors to twelve week-old renal cortices of Vhl-/-;Pbrm1-/- mice detected hyperactive mTORC1 signaling in tumors in addition to the demonstrated pre-existing activation of HIF/STAT and suppression of mitochondrial pathways [42]. Here, VHL is linked to nonpapillary renal cell carcinoma.