SWI/SNF deficient tumors – morphology, immunophenotype, genetics, epigenetics, nosology and therapy

About 20% of human cancers harbor mutations of genes encoding SWI/SNF (Switch/Sucrose Non-Fermentable) complex subunits. Deficiency of subunits of the complex is present in 10% non-small cell lung cancers (NSCLC; SMARCA4/SMARCA2 deficient), 100% thoracic SMARCA4/A2 deficient undifferentiated tumors (TSADUDT; SMARCA4/A2 deficient), malignant rhabdoid tumor (MRT) and atypical/teratoid tumor (AT/RT) (SMARCB1 deficient), >90% of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT; SMARCA4/SMARCA2 deficient), frequently in undifferentiated/dedifferentiated endometrial carcinoma (UDEC/DDEC; SMARCA4, SMARCA2, SMARCB1, ARID1A/B deficient), 100% SMARCA4 deficient undifferentiated uterine sarcoma (SDUS; SMARCA4 deficient); and in various other tumors from multifarious anatomic sites. Silencing of SWI/SNF gene expression may be genomically or epigenetically driven, causing loss of tumor suppression function or facilitating other oncogenic events. The SWI/SNF deficient tumors share the phenotype of poor or no differentiation, often with a variable component of rhabdoid tumor cells. They present at advanced stages with poor prognosis. Rhabdoid tumor cell phenotype is a useful feature to prompt investigation for this group of tumors. In the thoracic space, the overlap in morphology, immunophenotype, genetics, and epigenetics of SMARCA4/A2 deficient NSCLC and TSADUDT appears more significant. This raises a possible nosological relationship between TSADUDT and SMARCA4/A2 deficient NSCLC. Increased understanding of the genetics, epigenetics, and mechanisms of oncogenesis in these poor prognostic tumors, which are often resistant to conventional treatment, opens a new horizon of therapy for the tumors.About 20% of human cancers harbor mutations of genes encoding SWI/SNF (Switch/Sucrose Non-Fermentable) complex subunits. Deficiency of subunits of the complex is present in 10% non-small cell lung cancers (NSCLC; SMARCA4/SMARCA2 deficient), 100% thoracic SMARCA4/A2 deficient undifferentiated tumors (TSADUDT; SMARCA4/A2 deficient), malignant rhabdoid tumor (MRT) and atypical/teratoid tumor (AT/RT) (SMARCB1 deficient), >90% of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT; SMARCA4/SMARCA2 deficient), frequently in undifferentiated/dedifferentiated endometrial carcinoma (UDEC/DDEC; SMARCA4, SMARCA2, SMARCB1, ARID1A/B deficient), 100% SMARCA4 deficient undifferentiated uterine sarcoma (SDUS; SMARCA4 deficient); and in various other tumors from multifariou