Introduction: The route to precision medicine in Renal Cell Carcinoma (RCC) is still full of challenges for worldwide uro-oncologists. This is mainly related to the high complexity of the genomic landscape of this tumor. Area covered: In this review, we focused on the most recent advances on RCC genomic scenario and its clinical and prognostic implications. In particular, we describe the main gene alterations that occur during RCC development and progression. At this purpose, we extensively analyzed the available literature from Pubmed archives on this field. Expert commentary: Summarizing all available data and taking separately each putative biomarker illustrated, we feel to conclude that there is a certain correlation between the alterations occurring in BAP1, PBMR1, and SETD2 genes and the prognosis of RCC patients. However, apart from this individual analysis, the mutational scenario in RCC seems to be even more intricate. The evolution of RCC will pass through the optimization of emerging laboratory techniques and to a progressive integration of these methodologies within daily clinical practice and in the context of randomized trials.
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