PBRM1 and neoplasm: Jonasch et al. found an association between the molecular abnormalities underlying ccRCCs and their timing and subdivided them into those that drive tumor initiation events (3p loss/5q gain, VHL mutation, VHL methylation), tumor progression (PBRM1/SETD2/BAP1 mutations, DNA repair defects, defects in mitosis) and those that confer lethality (PI3K pathway activation, 9p, 14q, 8q gain) [100].