Bap1 and Pbrm1: Determinants of Tumor Grade and mTOR Activation in VHL-Deficient Mouse Models of Renal Cell Carcinoma

Large genome sequencing efforts have identified frequent mutations in the histone-modifying and chromatin-remodeling genes and in clear cell renal cell carcinoma (ccRCC). In this issue of , Gu and colleagues model these genetic events in mice and report that dual inactivation of with either or results in faithful genetically engineered murine models of ccRCC. Moreover, their work establishes that and are determinants of tumor grade and mTORC1 activation and provocatively suggests that the cell of origin of ccRCC may lie in PAX8-expressing Bowman capsule cells. .