SWI/SNF complex-deficient undifferentiated/rhabdoid carcinomas of the gastrointestinal tract

Undifferentiated gastrointestinal tract carcinomas are rare highly aggressive neoplasms with frequent but not obligatory rhabdoid features. Recent studies showed loss of SMARCB1 (INI1), a core subunit of the SWI/SNF chromatin remodeling complex, in 50% of tested cases. However, the molecular pathways underlying histologically similar but SMARCB1-intact cases are unknown.

Loss of different components of the SWI/SNF complex other than SMARCB1 can be observed in undifferentiated gastrointestinal carcinomas including novel SMARCA4-deficient and SMARCA2-deficient cases. It underlines the close link between SWI/SNF deficiency and the aggressive rhabdoid phenotype.

Frequent loss of SMARCA2 possibly points to fragility/vulnerability of the SWI/SNF complex as a consequence of lost core subunit SMARCB1. The exact molecular mechanisms underlying co-inactivation of different SWI/SNF subunits merit further investigations.

References

 SWI/SNF Complex-deficient Undifferentiated/Rhabdoid Carcinomas of the Gastrointestinal Tract: A Series of 13 Cases Highlighting Mutually Exclusive Loss of SMARCA4 and SMARCA2 and Frequent Co-inactivation of SMARCB1 and SMARCA2. Agaimy A, Daum O, Märkl B, Lichtmannegger I, Michal M, Hartmann A. Am J Surg Pathol. 2015 Nov 5. PMID: 26551623