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.
概要
子宫内膜间质肿瘤(EST)是一组较为少见的肿瘤,包括子宫内膜间质结节(ESN)、低级别子宫内膜间质肉瘤(LG-ESS)、高级别子宫内膜间质肉瘤(HG-ESS)和未分化子宫肉瘤(UUS),其中进展期LG-ESS、HG-ESS和UUS缺少有效的全身治疗。细胞遗传学和分子生物学研究发现,多数LG-ESS和所有HG-ESS携带再现性基因改变。本文重点描述了LG-ESS和HG-ESS中已知的再现性基因改变和相应的分子改变及其在肿瘤发生发展中的作用,总结了不同分子改变可能共享的信号途径及可作用的靶点,并提出针对可作用靶点、用于LG-ESS和HG-ESS全身治疗的策略
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References
Abu-Rustum NR, 2021. Uterine Neoplasms Version 1.2021. NCCN Clinical Practice Guidelines in Oncology. NCCN Guidelines®. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1473
Allen AJ, Ali SM, Gowen K, et al., 2017. A recurrent endometrial stromal sarcoma harbors the novel fusion JAZF1-BCORL1. Gynecol Oncol Rep, 20:51–53. https://doi.org/10.1016/j.gore.2017.03.002
Astolfi A, Fiore M, Melchionda F, et al., 2019. BCOR involvement in cancer. Epigenomics, 11(7):835–855. https://doi.org/10.2217/epi-2018-0195
Attar N, Kurdistani SK, 2017. Exploitation of EP300 and CREBBP lysine acetyltransferases by cancer. Cold Spring Harb Perspect Med, 7(3):a026534. https://doi.org/10.1101/cshperspect.a026534
Avvakumov N, Côté J, 2007. The MYST family of histone acetyltransferases and their intimate links to cancer. Oncogene, 26(37):5395–5407. https://doi.org/10.1038/sj.onc.1210608
Baek MH, Park JY, Rhim CC, et al., 2016. Immunohistochemical characterization of histone deacetylase as a potential prognostic marker and therapeutic target in endometrial stromal sarcoma. Anticancer Res, 36(5):2527–2534.
Birve A, Sengupta AK, Beuchle D, et al., 2001. Su(z)12, a novel Drosophila Polycomb group gene that is conserved in vertebrates and plants. Development, 128(17):3371–3379. https://doi.org/10.1242/dev.128.17.3371
Boudreault AA, Cronier D, Selleck W, et al., 2003. Yeast Enhancer of Polycomb defines global Esa1-dependent acetylation of chromatin. Genes Dev, 17(11):1415–1428. https://doi.org/10.1101/gad.1056603
Brandt LP, Albers J, Hejhal T, et al., 2017. Oncogenic HrasG12V expression plus knockdown of Cdkn2a using ecotropic lentiviral vectors induces high-grade endometrial stromal sarcoma. PLoS ONE, 12(10):e0186102. https://doi.org/10.1371/journal.pone.0186102
Brunet A, Kanai F, Stehn J, et al., 2002. 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport. J Cell Biol, 156(5):817–828. https://doi.org/10.1083/jcb.200112059
Brunetti M, Gorunova L, Davidson B, et al., 2018. Identification of an EPC2-PHF1 fusion transcript in low-grade endometrial stromal sarcoma. Oncotarget, 9(27):19203–19208. https://doi.org/10.18632/oncotarget.24969
Castañeda A, Serrano C, Hernández-Trejo JA, et al., 2017. pVHL suppresses Akt/β-catenin-mediated cell proliferation by inhibiting 14-3-3ζ expression. Biochem J, 474(16):2679–2689. https://doi.org/10.1042/BCJ20161097
Chamberlain PP, Hamann LG, 2019. Development of targeted protein degradation therapeutics. Nat Chem Biol, 15(10):937–944. https://doi.org/10.1038/s41589-019-0362-y
Chammas P, Mocavini I, di Croce L, 2020. Engaging chromatin: PRC2 structure meets function. Br J Cancer, 122(3):315–328. https://doi.org/10.1038/s41416-019-0615-2
Che XH, Chen H, Xu ZM, et al., 2010. 14-3-3epsilon contributes to tumour suppression in laryngeal carcinoma by affecting apoptosis and invasion. BMC Cancer, 10:306. https://doi.org/10.1186/1471-2407-10-306
Chen SM, Jiao LY, Shubbar M, et al., 2018. Unique structural platforms of Suz12 dictate distinct classes of PRC2 for chromatin binding. Mol Cell, 69(5):840–852.e5. https://doi.org/10.1016/j.molcel.2018.01.039
Chiang S, Ali R, Melnyk N, et al., 2011. Frequency of known gene rearrangements in endometrial stromal tumors. Am J Surg Pathol, 35(9):1364–1372. https://doi.org/10.1097/PAS.0b013e3182262743
Chiang S, Lee CH, Stewart CJR, et al., 2017. BCOR is a robust diagnostic immunohistochemical marker of genetically diverse high-grade endometrial stromal sarcoma, including tumors exhibiting variant morphology. Mod Pathol, 30(9):1251–1261. https://doi.org/10.1038/modpathol.2017.42
Choi J, Bachmann AL, Tauscher K, et al., 2017. DNA binding by PHF1 prolongs PRC2 residence time on chromatin and thereby promotes H3K27 methylation. Nat Struct Mol Biol, 24(12):1039–1047. https://doi.org/10.1038/nsmb.3488
Choi YJ, Jung SH, Kim MS, et al., 2015. Genomic landscape of endometrial stromal sarcoma of uterus. Oncotarget, 6(32):33319–33328. https://doi.org/10.18632/oncotarget.5384
Conklin CMJ, Longacre TA, 2014. Endometrial stromal tumors: the new WHO classification. Adv Anat Pathol, 21(6):383–393. https://doi.org/10.1097/PAP.0000000000000046
Conway SJ, 2020. Bifunctional molecules beyond PROTACs. J Med Chem, 63(6):2802–2806. https://doi.org/10.1021/acs.jmedchem.0c00293
Cossu-Rocca P, Contini M, Uras MG, et al., 2012. Tyrosine kinase receptor status in endometrial stromal sarcoma: an immunohistochemical and genetic-molecular analysis. Int J Gynecol Pathol, 31(6):570–579. https://doi.org/10.1097/PGP.0b013e31824fe289
Cotzia P, Benayed R, Mullaney K, et al., 2019. Undifferentiated uterine sarcomas represent under-recognized high-grade endometrial stromal sarcomas. Am J Surg Pathol, 43(5):662–669. https://doi.org/10.1097/PAS.0000000000001215
Deshmukh U, Black J, Perez-Irizarry J, et al., 2019. Adjuvant hormonal therapy for low-grade endometrial stromal sarcoma. Reprod Sci, 26(5):600–608. https://doi.org/10.1177/1933719118778801
Dewaele B, Przybyl J, Quattrone A, et al., 2014. Identification of a novel, recurrent MBTD1-CXorf67 fusion in low-grade endometrial stromal sarcoma. Int J Cancer, 134(5):1112–1122. https://doi.org/10.1002/ijc.28440
Dickson BC, Lum A, Swanson D, et al., 2018. Novel EPC1 gene fusions in endometrial stromal sarcoma. Genes Chromosomes Cancer, 57(11):598–603. https://doi.org/10.1002/gcc.22649
Eryilmaz J, Pan P, Amaya MF, et al., 2009. Structural studies of a four-MBT repeat protein MBTD1. PLoS ONE, 4(10):e7274. https://doi.org/10.1371/journal.pone.0007274
Ferreira J, Félix A, Lennerz JK, et al., 2018. Recent advances in the histological and molecular classification of endometrial stromal neoplasms. Virchows Arch, 473(6):665–678. https://doi.org/10.1007/s00428-018-2470-6
Fröhlich LF, Mrakovcic M, Smole C, et al., 2014. Epigenetic silencing of apoptosis-inducing gene expression can be efficiently overcome by combined SAHA and TRAIL treatment in uterine sarcoma cells. PLoS ONE, 9(3):e91558. https://doi.org/10.1371/journal.pone.0091558
Froimchuk E, Jang Y, Ge K, 2017. Histone H3 lysine 4 methyltransferase KMT2D. Gene, 627:337–342. https://doi.org/10.1016/j.gene.2017.06.056
Han LS, Liu YJ, Ricciotti RW, et al., 2020. A novel MBTD1-PHF1 gene fusion in endometrial stromal sarcoma: a case report and literature review. Genes Chromosomes Cancer, 59(7):428–432. https://doi.org/10.1002/gcc.22845
Harb M, Becker MM, Vitour D, et al., 2008. Nuclear localization of cytoplasmic poly(A)-binding protein upon rotavirus infection involves the interaction of NSP3 with eIF4G and RoXaN. J Virol, 82(22):11283–11293. https://doi.org/10.1128/JVI.00872-08
Hashizume R, Andor N, Ihara Y, et al., 2014. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat Med, 20(12):1394–1396. https://doi.org/10.1038/nm.3716
Hassan AH, Prochasson P, Neely KE, et al., 2002. Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell, 111(3):369–379. https://doi.org/10.1016/s0092-8674(02)01005-x
Hennig Y, Caselitz J, Bartnitzke S, et al., 1997. A third case of a low-grade endometrial stromal sarcoma with a t(7; 17) (p14∼21;q11.2∼21). Cancer Genet Cytogenet, 98(1):84–86. https://doi.org/10.1016/s0165-4608(96)00393-7
Hoang LN, Aneja A, Conlon N, et al., 2017. Novel high-grade endometrial stromal sarcoma: a morphologic mimicker of myxoid leiomyosarcoma. Am J Surg Pathol, 41(1):12–24. https://doi.org/10.1097/PAS.0000000000000721
Hrzenjak A, 2016. JAZF1/SUZ12 gene fusion in endometrial stromal sarcomas. Orphanet J Rare Dis, 11:15. https://doi.org/10.1186/s13023-016-0400-8
Hrzenjak A, Moinfar F, Kremser ML, et al., 2006. Valproate inhibition of histone deacetylase 2 affects differentiation and decreases proliferation of endometrial stromal sarcoma cells. Mol Cancer Ther, 5(9):2203–2210. https://doi.org/10.1158/1535-7163.MCT-05-0480
Hsu JHR, Rasmusson T, Robinson J, et al., 2020. EED-targeted PROTACs degrade EED, EZH2, and SUZ12 in the PRC2 complex. Cell Chem Biol, 27(1):41–46.e17. https://doi.org/10.1016/j.chembiol.2019.11.004
Hübner JM, Müller T, Papageorgiou DN, et al., 2019. EZHIP/CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma. Neuro-Oncol, 21(7):878–889. https://doi.org/10.1093/neuonc/noz058
Hung MC, Link W, 2011. Protein localization in disease and therapy. J Cell Sci, 124(Pt 20):3381–3392. https://doi.org/10.1242/jcs.089110
Jacquet K, Fradet-Turcotte A, Avvakumov N, et al., 2016. The TIP60 complex regulates bivalent chromatin recognition by 53BP1 through direct H4K20me binding and H2AK15 acetylation. Mol Cell, 62(3):409–421. https://doi.org/10.1016/j.molcel.2016.03.031
Kalender ME, Sevinc A, Yilmaz M, et al., 2009. Detection of complete response to imatinib mesylate (Glivec®/Gleevec®) with 18F-FDG PET/CT for low-grade endometrial stromal sarcoma. Cancer Chemother Pharmacol, 63(3):555–559. https://doi.org/10.1007/s00280-008-0786-7
Kao YC, Sung YS, Argani P, et al., 2020. NTRK3 overexpression in undifferentiated sarcomas with YWHAE and BCOR genetic alterations. Mod Pathol, 33(7):1341–1349. https://doi.org/10.1038/s41379-020-0495-2
Kenny C, McDonagh N, Lazaro A, et al., 2018. Dysregulated mitogen-activated protein kinase signalling as an oncogenic basis for clear cell sarcoma of the kidney. J Pathol, 244(3):334–345. https://doi.org/10.1002/path.5020
Khotskaya YB, Holla VR, Farago AF, et al., 2017. Targeting TRK family proteins in cancer. Pharmacol Ther, 173:58–66. https://doi.org/10.1016/j.pharmthera.2017.02.006
Kim KO, Hsu AC, Lee HG, et al., 2014. Proteomic identification of 14-3-3ϵ as a linker protein between pERK1/2 inhibition and BIM upregulation in human osteosarcoma cells. J Orthop Res, 32(6):848–854. https://doi.org/10.1002/jor.22598
Kommoss FKF, Stichel D, Schrimpf D, et al., 2020a. DNA methylation-based profiling of uterine neoplasms: a novel tool to improve gynecologic cancer diagnostics. J Cancer Res Clin Oncol, 146(1):97–104. https://doi.org/10.1007/s00432-019-03093-w
Kommoss FKF, Chang KTE, Stichel D, et al., 2020b. Endometrial stromal sarcomas with BCOR-rearrangement harbor MDM2 amplifications. J Pathol Clin Res, 6(3):178–184. https://doi.org/10.1002/cjp2.165
Lai AC, Toure M, Hellerschmied D, et al., 2016. Modular PROTAC design for the degradation of oncogenic BCR-ABL. Angew Chem Int Ed Engl, 55(2):807–810. https://doi.org/10.1002/anie.201507634
Leal MF, Ribeiro HF, Rey JA, et al., 2016. YWHAE silencing induces cell proliferation, invasion and migration through the up-regulation of CDC25B and MYC in gastric cancer cells: new insights about YWHAE role in the tumor development and metastasis process. Oncotarget, 7(51):85393–85410. https://doi.org/10.18632/oncotarget.13381
Lee CH, Ou WB, Mariño-Enriquez A, et al., 2012. 14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma. Proc Natl Acad Sci USA, 109(3):929–934. https://doi.org/10.1073/pnas.1115528109
Lee CH, Hoang LN, Yip S, et al., 2014. Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement. Mod Pathol, 27(5):751–757. https://doi.org/10.1038/modpathol.2013.199
Lee W, Teckie S, Wiesner T, et al., 2014. PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Genet, 46(11):1227–1232. https://doi.org/10.1038/ng.3095
Lewis N, Soslow RA, Delair DF, et al., 2018. ZC3H7B-BCOR high-grade endometrial stromal sarcomas: a report of 17 cases of a newly defined entity. Mod Pathol, 31(4):674–684. https://doi.org/10.1038/modpathol.2017.162
Li H, Ma XY, Wang JL, et al., 2007. Effects of rearrangement and allelic exclusion of JJAZ1/SUZ12 on cell proliferation and survival. Proc Natl Acad Sci USA, 104(50):20001–20006. https://doi.org/10.1073/pnas.0709986104
Liang SF, Xu YH, Shen GB, et al., 2009. Quantitative protein expression profiling of 14-3-3 isoforms in human renal carcinoma shows 14-3-3 epsilon is involved in limitedly increasing renal cell proliferation. Electrophoresis, 30(23):4152–4162. https://doi.org/10.1002/elps.200900249
Lin DI, Hemmerich A, Edgerly C, et al., 2020. Genomic profiling of BCOR-rearranged uterine sarcomas reveals novel gene fusion partners, frequent CDK4 amplification and CDKN2A loss. Gynecol Oncol, 157(2):357–366. https://doi.org/10.1016/j.ygyno.2020.02.024
Liu RQ, Gao J, Yang Y, et al., 2018. PHD finger protein 1 (PHF1) is a novel reader for histone H4R3 symmetric dimethylation and coordinates with PRMT5-WDR77/CRL4B complex to promote tumorigenesis. Nucleic Acids Res, 46(13):6608–6626. https://doi.org/10.1093/nar/gky461
Liu TA, Jan YJ, Ko BS, et al., 2013. 14-3-3ε overexpression contributes to epithelial-mesenchymal transition of hepatocellular carcinoma. PLoS ONE, 8(3):e57968. https://doi.org/10.1371/journal.pone.0057968
Ma XY, Wang JL, Wang JH, et al., 2017. The JAZF1-SUZ12 fusion protein disrupts PRC2 complexes and impairs chromatin repression during human endometrial stromal tumorogenesis. Oncotarget, 8(3):4062–4078. https://doi.org/10.18632/oncotarget.13270
Makise N, Sekimizu M, Kobayashi E, et al., 2019. Low-grade endometrial stromal sarcoma with a novel MEAF6-SUZ12 fusion. Virchows Arch, 475(4):527–531. https://doi.org/10.1007/s00428-019-02588-8
Mariño-Enriquez A, Lauria A, Przybyl J, et al., 2018. BCOR internal tandem duplication in high-grade uterine sarcomas. Am J Surg Pathol, 42(3):335–341. https://doi.org/10.1097/PAS.0000000000000993
Mauri D, Pavlidis N, Polyzos NP, et al., 2006. Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. J Natl Cancer Inst, 98(18):1285–1291. https://doi.org/10.1093/jnci/djj357
Mei JW, Yang ZY, Xiang HG, et al., 2019. MicroRNA-1275 inhibits cell migration and invasion in gastric cancer by regulating vimentin and E-cadherin via JAZF1. BMC Cancer, 19:740. https://doi.org/10.1186/s12885-019-5929-1
Micci F, Panagopoulos I, Bjerkehagen B, et al., 2006. Consistent rearrangement of chromosomal band 6p21 with generation of fusion genes JAZF1/PHF1 and EPC1/PHF1 in endometrial stromal sarcoma. Cancer Res, 66(1):107–112. https://doi.org/10.1158/0008-5472.CAN-05-2485
Micci F, Gorunova L, Gatius S, et al., 2014. MEAF6/PHF1 is a recurrent gene fusion in endometrial stromal sarcoma. Cancer Lett, 347(1):75–78. https://doi.org/10.1016/j.canlet.2014.01.030
Micci F, Brunetti M, dal Cin P, et al., 2017. Fusion of the genes BRD8 and PHF1 in endometrial stromal sarcoma. Genes Chromosomes Cancer, 56(12):841–845. https://doi.org/10.1002/gcc.22485
Monden T, Wondisford FE, Hollenberg AN, 1997. Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein. J Biol Chem, 272(47):29834–29841. https://doi.org/10.1074/jbc.272.47.29834
Oppel F, Ki DH, Zimmerman MW, et al., 2020. suz12 inactivation in p53- and nf1-deficient zebrafish accelerates the onset of malignant peripheral nerve sheath tumors and expands the spectrum of tumor types. Dis Model Mech, 13(8):dmm042341. https://doi.org/10.1242/dmm.042341
Panagopoulos I, Mertens F, Griffin CA, 2008. An endometrial stromal sarcoma cell line with the JAZF1/PHF1 chimera. Cancer Genet Cytogenet, 185(2):74–77. https://doi.org/10.1016/j.cancergencyto.2008.04.020
Panagopoulos I, Micci F, Thorsen J, et al., 2012. Novel fusion of MYST/Esa1-associated factor 6 and PHF1 in endometrial stromal sarcoma. PLoS ONE, 7(6):e39354. https://doi.org/10.1371/journal.pone.0039354
Panagopoulos I, Thorsen J, Gorunova L, et al., 2013. Fusion of the ZC3H7B and BCOR genes in endometrial stromal sarcomas carrying an X; 22-translocation. Genes Chromosomes Cancer, 52(7):610–618. https://doi.org/10.1002/gcc.22057
Patel RB, Li T, Liao Z, et al., 2017. Recent translational research into targeted therapy for liposarcoma. Stem Cell Investig, 4:21. https://doi.org/10.21037/sci.2017.02.09
Patel SB, McCormack C, Hodge JC, 2020. Non-fusion mutations in endometrial stromal sarcomas: what is the potential impact on tumourigenesis through cell cycle dysregulation? J Clin Pathol, 73(12):830–835. https://doi.org/10.1136/jclinpath-2020-206432
Piunti A, Smith ER, Morgan MAJ, et al., 2019. CATACOMB: an endogenous inducible gene that antagonizes H3K27 methylation activity of Polycomb repressive complex 2 via an H3K27M-like mechanism. Sci Adv, 5(7):eaax2887. https://doi.org/10.1126/sciadv.aax2887
Potjewyd F, Turner AMW, Beri J, et al., 2020. Degradation of polycomb repressive complex 2 with an EED-targeted bivalent chemical degrader. Cell Chem Biol, 27(1):47–56.e15. https://doi.org/10.1016/j.chembiol.2019.11.006
Prieto-Granada CN, Wiesner T, Messina JL, et al., 2016. Loss of H3K27me3 expression is a highly sensitive marker for sporadic and radiation-induced MPNST. Am J Surg Pathol, 40(4):479–489. https://doi.org/10.1097/PAS.0000000000000564
Przybyl J, Kidzinski L, Hastie T, et al., 2018. Gene expression profiling of low-grade endometrial stromal sarcoma indicates fusion protein-mediated activation of the Wnt signaling pathway. Gynecol Oncol, 149(2):388–393. https://doi.org/10.1016/j.ygyno.2018.03.007
Qin JZ, Whyte WA, Anderssen E, et al., 2012. The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development. Cell Stem Cell, 11(3):319–332. https://doi.org/10.1016/j.stem.2012.06.002
Quan P, Moinfar F, Kufferath I, et al., 2014. Effects of targeting endometrial stromal sarcoma cells via histone deacetylase and PI3K/AKT/mTOR signaling. Anticancer Res, 34(6):2883–2897.
Rubin JB, Segal RA, 2003. Growth, survival and migration: the Trk to cancer. Cancer Treat Res, 115:1–18. https://doi.org/10.1007/0-306-48158-8_1
Salvatierra A, Tarrats A, Gomez C, et al., 2006. A case of c-kit positive high-grade stromal endometrial sarcoma responding to Imatinib Mesylate. Gynecol Oncol, 101(3):545–547. https://doi.org/10.1016/j.ygyno.2006.01.024
Sarma K, Margueron R, Ivanov A, et al., 2008. Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo. Mol Cell Biol, 28(8):2718–2731. https://doi.org/10.1128/MCB.02017-07
Schoolmeester JK, Sciallis AP, Greipp PT, et al., 2015. Analysis of MDM2 amplification in 43 endometrial stromal tumors: a potential diagnostic pitfall. Int J Gynecol Pathol, 34(6):576–583. https://doi.org/10.1097/PGP.0000000000000187
Seagle BLL, Shilpi A, Buchanan S, et al., 2017. Low-grade and high-grade endometrial stromal sarcoma: a National Cancer Database study. Gynecol Oncol, 146(2):254–262. https://doi.org/10.1016/j.ygyno.2017.05.036
Serkies K, Abacjew-Chmyłko A, Wieczorek-Rutkowska M, et al., 2018. Aromatase inhibitor therapy for endometrial stromal sarcoma—two-centre experience. Ginekol Pol, 89(11):607–610. https://doi.org/10.5603/GP.a2018.0104
Spring LM, Wander SA, Andre F, et al., 2020. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future. Lancet, 395(10226):817–827. https://doi.org/10.1016/S0140-6736(20)30165-3
Sreekantaiah C, Li FP, Weidner N, et al., 1991. An endometrial stromal sarcoma with clonal cytogenetic abnormalities. Cancer Genet Cytogenet, 55(2):163–166. https://doi.org/10.1016/0165-4608(91)90073-4
Stankunas K, Berger J, Ruse C, et al., 1998. The Enhancer of Polycomb gene of Drosophila encodes a chromatin protein conserved in yeast and mammals. Development, 125(20):4055–4066. https://doi.org/10.1242/dev.125.20.4055
Studach LL, Menne S, Cairo S, et al., 2012. Subset of Suz12/PRC2 target genes is activated during hepatitis B virus replication and liver carcinogenesis associated with HBV X protein. Hepatology, 56(4):1240–1251. https://doi.org/10.1002/hep.25781
Sung Y, Park S, Park SJ, et al., 2018. Jazf1 promotes prostate cancer progression by activating JNK/Slug. Oncotarget, 9(1):755–765. https://doi.org/10.18632/oncotarget.23146
Thiel FC, Halmen S, 2018. Low-grade endometrial stromal sarcoma—a review. Oncol Res Treat, 41(11):687–692. https://doi.org/10.1159/000494225
Uchida C, Miwa S, Kitagawa K, et al., 2005. Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation. EMBO J, 24(1):160–169. https://doi.org/10.1038/sj.emboj.7600486
Ueyama M, Nishida N, Korenaga M, et al., 2016. The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus. J Gastroenterol, 51(4):370–379. https://doi.org/10.1007/s00535-015-1116-6
Verschoor AJ, Warmerdam FARM, Bosse T, et al., 2018. A remarkable response to pazopanib, despite recurrent liver toxicity, in a patient with a high grade endometrial stromal sarcoma, a case report. BMC Cancer, 18:92. https://doi.org/10.1186/s12885-018-3999-0
Vilgelm AE, Saleh N, Shattuck-Brandt R, et al., 2019. MDM2 antagonists overcome intrinsic resistance to CDK4/6 inhibition by inducing p21. Sci Transl Med, 11(505):eaav7171. https://doi.org/10.1126/scitranslmed.aav7171
Wade M, Li YC, Matani AS, et al., 2012. Functional analysis and consequences of Mdm2 E3 ligase inhibition in human tumor cells. Oncogene, 31(45):4789–4797. https://doi.org/10.1038/onc.2011.625
Wienken M, Dickmanns A, Nemajerova A, et al., 2016. MDM2 associates with polycomb repressor complex 2 and enhances stemness-promoting chromatin modifications independent of p53. Mol Cell, 61(1):68–83. https://doi.org/10.1016/j.molcel.2015.12.008
Wong SJ, Senkovich O, Artigas JA, et al., 2020. Structure and role of BCOR PUFD in noncanonical PRC1 assembly and disease. Biochemistry, 59(29):2718–2728. https://doi.org/10.1021/acs.biochem.0c00285
Xu Y, Fulciniti M, Samur MK, et al., 2020. YWHAE/14-3-3ε expression impacts the protein load, contributing to proteasome inhibitor sensitivity in multiple myeloma. Blood, 136(4):468–479. https://doi.org/10.1182/blood.2019004147
Yang YF, Lee YC, Wang YY, et al., 2019. YWHAE promotes proliferation, metastasis, and chemoresistance in breast cancer cells. Kaohsiung J Med Sci, 35(7):408–416. https://doi.org/10.1002/kjm2.12075
Yao WJ, Tong S, Tan J, et al., 2019. NF45 promotes esophageal squamous carcinoma cell invasion by increasing Rac1 activity through 14-3-3ε protein. Arch Biochem Biophys, 663:101–108. https://doi.org/10.1016/j.abb.2018.12.012
Zhang CW, Han XR, Yang XB, et al., 2018. Proteolysis targeting chimeras (PROTACs) of anaplastic lymphoma kinase (ALK). Eur J Med Chem, 151:304–314. https://doi.org/10.1016/j.ejmech.2018.03.071
Zhang H, Devoucoux M, Song XS, et al., 2020. Structural basis for EPC1-mediated recruitment of MBTD1 into the NuA4/TIP60 acetyltransferase complex. Cell Rep, 30(12):3996–4002.e4. https://doi.org/10.1016/j.celrep.2020.03.003
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This work was supported by the WU JIEPING MEDICAL FOUNDATION (No. 320.6750.18489), China.
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Chunhong WANG conducted this review. Chunhong WANG and Chunhui LI contributed to the writing and editing of the manuscript. Both authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Chunhui LI and Chunhong WANG declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by either of the authors.
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Li, C., Wang, C. LG-ESSs and HG-ESSs: underlying molecular alterations and potential therapeutic strategies. J. Zhejiang Univ. Sci. B 22, 633–646 (2021). https://doi.org/10.1631/jzus.B2000797
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DOI: https://doi.org/10.1631/jzus.B2000797
Key words
- Low-grade endometrial stromal sarcoma (LG-ESS)
- High-grade endometrial stromal sarcoma (HG-ESS)
- Molecular genetics
- Therapeutics