Abstract 1807 Polybromo-1 bromodomain missense variants associated with clear cell renal cell carcinoma exhibit variable biochemical fitness

The tumor suppressor Polybromo-1 (PBRM1) modulates chromatin accessibility and gene transcription in health and disease. PBRM1 contains six bromodomains that bind acetylated lysine residues on histones and other nuclear proteins. PBRM1 mutations, which often ablate protein expression and tumor suppressor activity, exist in ∼40% of clear cell renal cell carcinoma (ccRCC) cases. Loss-of-function PBRM1 mutations correlate with improved patient response to anti-angiogenic agents, a mainstay of ccRCC therapy.