Additionally, according to the TRACERx Renal study, in which ccRCC biopsies were collected from 33 patients using a multi-region sampling approach, loss of 3p usually occurs first through chromothripsis, with VHL inactivation as a second event due to either VHL mutation or the hypermethylation of the VHL promoter region [14]. Here, VHL is linked to nonpapillary renal cell carcinoma.