Expanding the molecular spectrum of gene fusions in endometrial stromal sarcoma: Novel subunits of the chromatin remodeling complexes PRC2 and NuA4/TIP60 as alternative fusion partners Journal Article
| Authors: | Dermawan, J. K.; Dashti, N.; Chiang, S.; Turashvili, G.; Dickson, B. C.; Ellenson, L. H.; Kirchner, M.; Stenzinger, A.; Mechtersheimer, G.; Agaimy, A.; Antonescu, C. R. |
| Article Title: | Expanding the molecular spectrum of gene fusions in endometrial stromal sarcoma: Novel subunits of the chromatin remodeling complexes PRC2 and NuA4/TIP60 as alternative fusion partners |
| Abstract: | Endometrial stromal sarcomas (ESS) are morphologically and molecularly heterogeneous. We report novel gene fusions (EPC1::EED, EPC1::EZH2, ING3::PHF1) identified by targeted RNA sequencing in five cases. The ING3::PHF1-fusion positive ESS presented in a 58-year-old female as extrauterine mesocolonic, ovarian masses, and displayed large, monomorphic ovoid-to-epithelioid cells arranged in solid sheets. The patient remained alive with disease 13 months after surgery. The three ESS with EPC1::EED occurred in the uterine corpus in patients with a median age of 58 years (range 27-62 years). One tumor showed a uniform epithelioid nested morphology, while the other two were composed of monomorphic spindle cells in fascicles with elevated mitotic figures, focal tumor cell necrosis, and lymphovascular invasion. At a median follow-up of 20 months, two patients developed local recurrence, including one with concomitant distant metastasis, while one patient remained free of disease. All three patients were alive at the last follow-up. The EPC1::EZH2-fusion positive ESS presented in a 52-year-old female in the uterus, and displayed uniform spindled cells arranged in short fascicles, with focally elevated mitotic activity but without necrosis. The patient remained free of disease 3 months after surgery. All cases were diffusely positive for CD10; four diffusely express estrogen and progesterone receptors. Our study expands the molecular spectrum of EPC1 and PHF1-related gene fusions in ESS to include additional novel subunits of the PRC2 and/or NuA4/TIP60 complexes. These cases displayed a monomorphic epithelioid or spindled phenotype, spanning low-grade and high-grade cytomorphology, all expressing CD10 and commonly ER and PR, and are prone to local and/or distant spread. |
| Keywords: | methylation; neoplasms; sarcomas; differentiation; gene fusions; generation; rearrangements; uterine; smooth-muscle tumors; frequency; endometrial stromal sarcoma; ezh2; high-grade; internal tandem duplication; eed; phf1; epc1; ing3 |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 62 |
| Issue: | 3 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2023-03-01 |
| Start Page: | 152 |
| End Page: | 160 |
| Language: | English |
| ACCESSION: | WOS:000893938800001 |
| DOI: | 10.1002/gcc.23109 |
| PROVIDER: | wos |
| PMCID: | PMC9825654 |
| PUBMED: | 36445224 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF --Corresponding author is MSK author: Cristina R. Antonescu -- Source: Wos |
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