Beyond SMARCB1 Loss: Recent Insights into the Pathobiology of Epithelioid Sarcoma

Cells. 2022 Aug 24;11(17):2626. doi: 10.3390/cells11172626.

Abstract

Epithelioid sarcoma (ES) is a very rare and aggressive mesenchymal tumor of unclear origin and uncertain lineage characterized by a prevalent epithelioid morphology. The only recurrent genetic alteration reported in ES as yet is the functional inactivation of SMARCB1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1), a key component of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complexes. How SMARCB1 deficiency dictates the clinicopathological characteristics of ES and what other molecular defects concur to its malignant progression is still poorly understood. This review summarizes the recent findings about ES pathobiology, including defects in chromatin remodeling and other signaling pathways and their role as therapeutic vulnerabilities.

Keywords: PRC2 (Polycomb Repressive Complex 2); SMARCB1; SWI/SNF; epithelioid sarcoma; soft tissue sarcoma; tazemetostat.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins* / metabolism
  • Humans
  • SMARCB1 Protein / genetics
  • SMARCB1 Protein / metabolism
  • Sarcoma* / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors

Grants and funding

This work was supported by the Italian Ministry of Health; Alleanza Contro il Cancro (ACC) Sarcoma WG; Associazione Italiana Ricerca sul Cancro (AIRC #19975) to R.M.