PBRM1 and nonpapillary renal cell carcinoma: Thus, CCRCC characterized by low chromosomal complexity and low intratumor heterogeneity evolves following a linear pathway with VHL as sole mutation; CCRCC evolving through a branched pathway acquires early PBRM1 mutation and subsequent subclonal driver alterations slowly evolves to a oligometastatic potential; CCRCC evolving through a punctuated pathway results from the development of tumors characterized by the presence of multiple driver genetic alterations occurring clonally (punctuated evolution) and evolves more rapidly to metastatic potential [178] (Table 3).