SETD2 and cancer: Notably, clear cell RCC is associated with cytogenetic loss of chromosome 3p, encompassing four of the most commonly mutated genes in this cancer: the closely linked Von Hippel–Lindau (VHL) tumor suppressor gene which has been identified to be inactivated in up to 92% of cases 5, and the more recently recognized high-frequency mutations in PBRM1 (polybromo 1), BAP1 [BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase)], and SETD2 (SET domain containing 2) 6–8.