Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness

Abstract

Aneuploidy results in decreased cellular fitness in many species and model systems. However, aneuploidy is commonly found in cancer cells and often correlates with aggressive growth, suggesting that the impact of aneuploidy on cellular fitness is context dependent. The BRG1 (SMARCA4) subunit of the SWI/SNF chromatin remodelling complex is frequently lost in cancer. Here, the authors show that BRG1 loss can lead to changes that allow tolerance to aneuploidy. This creates a setting where karyotype changes can be explored without a fitness penalty, allowing adaptation to changing environments. This could play an important role in the progression of BRG1 deficient cancers.