S/R RCC tumors have a distinctive genomic profile characterized by an enrichment for genomic alterations previously associated with poor prognosis in RCC (such as BAP1 and CDKN2A) and genomic alterations that may represent therapeutic targets in S/R RCC (CDKN2A and CDKN2B deletions, EZH2 amplifications, and NF2 mutations). Here, EZH2 is linked to renal cell carcinoma.