TSC1 and renal cell carcinoma: In melanoma-prone families, predisposing genes target the cell cycle (CDKN2A, CDK4) or telomere regulation (ACD, POT1, TERF2IP, TERT) [18] whereas RCC predisposing genes target mainly metabolism, in particular, the Akt/HIF pathway (FH, FLCN, MET, PTEN, SDHs, TSC1, TSC2, and VHL), and epigenome regulation (PBRM1 and BAP1).