PBRM1 is second most commonly mutated gene (35%) in primary clear cell renal cell carcinoma after VHL. This locus encodes a subunit of ATP-dependent chromatin-remodeling complexes. The encoded protein has been identified as in integral component of complexes necessary for ligand-dependent transcriptional activation by nuclear hormone receptors. PBRM1 is likely a tumor suppressor because the reported mutations are mostly inactivating truncations. PBRM1 mutations, similar to those of VHL, occur early in ccRCC tumorigenesis, with mutations being present in all cancer cells within a tumor in many cases. The contribution of PBRM1 mutations to the clinical outcome of ccRCC patients has been controversial. Some groups reported that these mutations did not seem to correlate with adverse patient survival. However, other groups have reported that PBRM1mutations are positively linked to tumor invasiveness and, based on immunohistochemistry findings, loss of the PBRM1 protein was associated with advanced tumor stage, high Fuhrman grade, and poor overall survival.

This gene is a known cancer gene.

This gene is a known cancer gene.