BAP1 loss defines a new class of renal cell carcinoma

James Brugarolas and colleagues identify recurrent BAP1 mutations in clear cell renal cell carcinoma (ccRCC). They show that BAP1 binds to HCF-1 and suppresses cell proliferation, and they find that BAP1 loss is associated with high tumor grade. The molecular pathogenesis of renal cell carcinoma (RCC) is poorly understood. Whole-genome and exome sequencing followed by innovative tumorgraft analyses (to accurately determine mutant allele ratios) identified several putative two-hit tumor suppressor genes, including BAP1. The BAP1 protein, a nuclear deubiquitinase, is inactivated in 15% of clear cell RCCs. BAP1 cofractionates with and binds to HCF-1 in tumorgrafts. Mutations disrupting the HCF-1 binding motif…

• UO
  University of Texas Southwestern Medical Center