SETD2 and nonpapillary renal cell carcinoma: However, ccRCC is a highly genetically heterogeneous disease, in a study of four patients with ccRCC who had multiple tumors were subjected to multi-region genetic analysis, common driver events such as SETD2 , PBRM1 , MTOR , PIK3CA, PTEN and KDM5C mutations were observed heterogeneously within the primary tumour and metastatic sites - in some regions but not others 9.