The genetic profile of RCC subtypes, including p53 [12–19] (see Table 1) might include PBRM1 mutations, that display upregulation of several genes involved in the angiogenesis, with increased response to VEGF-target therapy [20], VHL-deficiency in RCC is associated to a vascular development gene expression signature triggered by VHL/HIF pathway which can be target by HIF-2a inhibitors [21] while increased TH2 immune gene expression signature is strongly associated to poor prognosis and lower survival [22]. The gene discussed is TP53; the disease is renal cell carcinoma.