BAFfling pathologies: Alterations of BAF complexes in cancer

Abstract

To activate or repress specific genes, chromatin is constantly modified by chromatin-remodeling complexes. Among these complexes, the SWItch/Sucrose Non-Fermenting (SWI/SNF) complex, also referred to as BRG1-Associated Factor (BAF) complex, moves the nucleosome along chromatin using energy provided by ATP hydrolysis. In mammalian organisms, the SWI/SNF complex is composed of 10–15 subunits, depending on cell type, and a defect in one of these subunits can have dramatic consequences. In this review we will focus on the alterations identified in the SWI/SNF (BAF) complex subunits that lead to cancerous pathologies. While SMARCB1 was the first mutated subunit to be reported in a majority of malignant rhabdoid tumors, the advent of next-generation sequencing allowed the discovery of mutations in various SWI/SNF subunits within a broad spectrum of cancers. In most cases, the mutation leads to a loss of expression or to a truncated subunit unable to perform its function. Even though it is now commonly acknowledged that approximately 20% of all cancers present a mutation in a SWI/SNF subunit, some cancers are associated to a specific alteration of a SWI/SNF subunit, which acts either as tumor suppressor genes or as oncogenes, and therefore constitute diagnostic or prognostic biomarkers. Consistently, therapeutic strategies targeting SWI/SNF subunits or the genes affected downstream have been revealed to treat cancers.