PBRM1 and nonpapillary renal cell carcinoma: In addition, analysis of mouse and human ccRCC has revealed that VHL and PBRM1 doubly deficient tumors displayed a convergence on the mTOR pathway activation after a long latency period, suggesting that the activation of mTOR serves as the third oncogenic driver event in ccRCC following the loss of VHL and PBRM1 [91].