**6. SWI/SNF**

SWI/SNF are mammalian homologs of yeast trithorax complexes. Their major purpose is to antagonize PRC-2's repressive effects by destroying DNA-nucleosome connections allowing movement and ejection, or by switching nucleosomes to increase factor accessibility transcription to DNA [84, 85]. In human malignancies, the genes encoding the SWI/SNF complexes are commonly altered, with various subunit mutations related to specific cancer histologies.

Yoshikawa et al. [86] used whole exome sequencing to identify a substantial number of mutations in genes involved in the SWI/SNF pathways, including homozygous SMARCA4, ARID2, and PBRM1 mutations in short-term established MPM lines [86, 87]. They also evaluated at the loss of somatic copies in the 3p21 region (which is roughly 10.7 Mb in size and contains 251 genes) in 33 MPM samples, using techniques including comparative genomic matrix high-density hybridization (a-CGH) and next-generation targeted sequencing (NGS). Bi-allelic deletions (3 Kb) were observed in 46 genes, four of which have been associated to malignant tumors, including two SWI/SNF-related genes [PBRM1 (15%) and SMARCC1 (6%)], BAP1 (48%) and SETD2 (27%). More than 200 MPM were studied in a recent thorough genomic investigation.

Bueno et al. [88] described mutations in genes encoding SWI/SNF components in 8% of the samples, as well as mutations in two histone methyltransferases (SETDB1 and SETD5) in about 3% of the samples. The discrepancies between the results reported by Yoshikawa et al. [87] and Bueno et al. [88] may be attributable to the identification of minuscule deletions by high-density, a-CGH, and specific NGS that are not detectable by conventional NGS techniques. To establish final conclusions, more studies are needed to determine the frequency and clinical significance of SWI/ SNF mutations in mesothelioma.
