LG-ESSs and HG-ESSs: underlying molecular alterations and potential therapeutic strategies

J Zhejiang Univ Sci B. 2021 Aug 15;22(8):633-646. doi: 10.1631/jzus.B2000797.

Abstract

Endometrial stromal tumors (ESTs) include endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). Since these are rare tumor types, there is an unmet clinical need for the systematic therapy of advanced LG-ESS or HG-ESS. Cytogenetic and molecular advances in ESTs have shown that multiple recurrent gene fusions are present in a large proportion of LG-ESSs, and HG-ESSs are identified by the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (YWHAE)-family with sequence similarity 22 (FAM22) fusion. Recently, a group of ESSs harboring both zinc finger CCCH domain-containing protein 7B (ZC3H7B)-B-cell lymphoma 6 corepressor(BCOR) fusion and internal tandem duplication (ITD) of the BCOR gene have been provisionally classified as HG-ESSs. In this review, we firstly describe current knowledge about the molecular characteristics of recurrent aberrant proteins and their roles in the tumorigenesis of LG-ESSs and HG-ESSs. Next, we summarize the possibly shared signal pathways in the tumorigenesis of LG-ESSs and HG-ESSs, and list potentially actionable targets. Finally, based on the above discussion, we propose a few promising therapeutic strategies for LG-ESSs and HG-ESSs with recurrent gene alterations.

Keywords: High-grade endometrial stromal sarcoma (HG-ESS); Low-grade endometrial stromal sarcoma (LG-ESS); Molecular genetics; Therapeutics.

Publication types

  • Review

MeSH terms

  • 14-3-3 Proteins
  • Carcinogenesis
  • Endometrial Neoplasms / classification*
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / therapy
  • Endometrial Stromal Tumors / genetics
  • Female
  • Gene Duplication
  • Humans
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • Sarcoma, Endometrial Stromal / genetics
  • Signal Transduction

Substances

  • 14-3-3 Proteins
  • BCOR protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • YWHAE protein, human
  • ZC3H7B protein, human