As with all genetic discoveries that have poured out of laboratories in recent years—from thousands of genes associated with rare Mendelian disorders and common disease to the hundreds that have been implicated in human cancer—driver, causative function is often challenging to assign, especially in the setting of tumors with numerous mutations. However, in certain tumors, specific genes are mutated in 100% of the cancers in 100% of the cells, which provides definitive evidence that these mutations cause the development and maintenance of the tumor. An example is human synovial sarcoma (88, 89), which has provided ground for the discovery of a mechanism underpinning perturbation to the SS18 subunit of BAF complexes by the t(X;18) translocation hallmark to human synovial sarcoma. This mechanism has been highly informative for understanding the emergence of specificity of actions of mSWI/SNF or BAF complexes.
