PBRM1: A critical subunit of the SWI/SNF chromatin remodeling complex

Rapid advances in genomics have altered the landscape of oncology by accelerating the identification of disease-related oncogenes and tumor suppressors. It has become increasingly evident that even within specific cancer types there is incredible genetic diversity and heterogeneity, which may help explain the variability of responses to therapy. Greater understanding of these genetic changes will help the development of personalized, targeted care for patients. Large-scale sequencing projects, surveying whole exomes of clear cell renal cell carcinoma (ccRCC) tumors, have recently identified several important tumor suppressor genes, including PBRM1, SETD2, BAP1, and KDM5C. These genes are guiding new directions for oncology research and providing intriguing insights into ccRCC tumorigenesis. Specifically, the identification of these genes has heightened interest over discovering clinically useful kidney cancer biomarkers. Also, they have triggered intensive efforts in basic science laboratories to elucidate the biological function behind each enigmatic gene, with a view toward refining paradigms that more accurately reflect ccRCC formation and disease progression, and for developing better strategies for patient care.This chapter summarizes the emerging information on these tumor suppressors, all of which appear to act as chromatin-modifying enzymes. We provide emphasis on the PBRM1 gene, identified as the most commonly mutated gene in ccRCC after the von Hippel-Lindau (VHL) tumor suppressor gene. We will also speculate on PBRM1‘s ability to serve as a novel molecular target for therapy. For this purpose, we offer a description of nucleosome remodeling enzymes with attention focused on the SWI/SNF complexes, of which PBRM1 participates as an important accessory protein component.