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

• Published in: Journal of Zhejiang University. B. Science Vol. 22; no. 8; pp. 633 - 646
• Main Authors: Li, Chunhui, Wang, Chunhong
• Format: Journal Article
• Language: English
• Published: Hangzhou Zhejiang University Press 01.07.2021; Springer Nature B.V; Quality Management Office,The Second Hospital of Jilin University,Changchun 130041,China%Department of Hematology and Oncology,The Second Hospital of Jilin University,Changchun 130041,China
• Subjects: 14-3-3 Proteins; B-cell lymphoma; Biomedical and Life Sciences; Biomedicine; Carcinogenesis; Cytogenetics; Endometrial Neoplasms - classification; Endometrial Neoplasms - genetics; Endometrial Neoplasms - therapy; Endometrial Stromal Tumors - genetics; Endometrium; Female; Gene Duplication; Humans; Lymphocytes B; Lymphoma; Oncogene Proteins, Fusion; Proteins; Proto-Oncogene Proteins; Repressor Proteins; Review; RNA-Binding Proteins; Sarcoma; Sarcoma, Endometrial Stromal - genetics; Signal Transduction; Tryptophan; Tryptophan 5-monooxygenase; Tumorigenesis; Tumors; Tyrosine; Tyrosine 3-monooxygenase; Uterus; Zinc finger proteins; 低级别子宫内膜间质肉瘤(LG-ESS); 治疗; Low-grade endometrial stromal sarcoma (LG-ESS); Molecular genetics; 高级别子宫内膜间质肉瘤(HG-ESS); 分子遗传学; Therapeutics; High-grade endometrial stromal sarcoma (HG-ESS)
• ISSN: 1673-1581; 1862-1783; 1862-1783
• DOI: 10.1631/jzus.B2000797

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.