Advertisement

Low-grade endometrial stromal sarcoma with a novel MEAF6-SUZ12 fusion

  • Naohiro Makise
  • Masaya Sekimizu
  • Eisuke Kobayashi
  • Hiroshi Yoshida
  • Masashi Fukayama
  • Tomoyasu Kato
  • Akira Kawai
  • Hitoshi Ichikawa
  • Akihiko YoshidaEmail author
Brief Report
  • 43 Downloads

Abstract

Endometrial stromal sarcoma (ESS) is a rare mesenchymal neoplasm. Herein, we report a low-grade ESS with a novel MEAF6-SUZ12 fusion gene. A 40-year-old woman presented with a 9.0-cm abdominal wall mass juxtaposed to the postoperative scar of surgeries for uterine “leiomyomas” and cesarean section. Histologically, mostly hypocellular and myxoid nodules were comprised of uniform spindle cells and exhibited tongue-like infiltration. Immunohistochemically, the tumor cells were positive for CD10, estrogen receptor, and CD34 (focal). There were occasional h-caldesmon-positive cohesive nests. RNA sequencing along with reverse transcriptase-polymerase chain reaction and Sanger sequencing identified an in-frame fusion of MEAF6 (exon 4) and SUZ12 (exon 2). Upon review of the previous “leiomyomas,” we revised their diagnoses as low-grade ESS. The patient is alive without disease 2 years after the surgery. In addition to expanding the molecular landscape of low-grade ESS, this case highlights the challenge of diagnosing low-grade ESS in an uncommon clinicopathological setting.

Keywords

Endometrial stromal sarcoma Histone modification MEAF6 Polycomb repressive complex SUZ12 

Notes

Acknowledgements

The authors thank Sachiko Miura, Toshiko Sakaguchi, Chizu Kina, and Sachiyo Mitani for superb technical assistance.

Author’s contributions

NM and AY conceived and designed the study, and wrote, edited, and reviewed the manuscript. NM, HY, and AY did histological assessment. MS and HI did molecular analyses. EK, TK, and AK collected clinical samples. MF supported the study. All authors gave final approval for publication.

Funding

This work was supported in part by JSPS Grant-in-Aid for Young Scientists (18K15108 and 18K15110), by a Grant-in-Aid for Practical Research for Innovative Cancer Control from AMED (17ck0106168h0003), and by a National Cancer Center Research and Development Fund (29-A-2).

Compliance with ethical standards

The study was approved by the institutional review board (2014–089).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Baker P, Oliva E (2007) Endometrial stromal tumours of the uterus: a practical approach using conventional morphology and ancillary techniques. J Clin Pathol 60:235–243CrossRefGoogle Scholar
  2. 2.
    Chiang S, Ali R, Melnyk N, McAlpine JN, Huntsman DG, Gilks CB, Lee CH, Oliva E (2011) Frequency of known gene rearrangements in endometrial stromal tumors. Am J Surg Pathol 35:1364–1372CrossRefGoogle Scholar
  3. 3.
    Micci F, Gorunova L, Agostini A, Johannessen LE, Brunetti M, Davidson B, Heim S, Panagopoulos I (2016) Cytogenetic and molecular profile of endometrial stromal sarcoma. Genes Chromosom Cancer 55:834–846CrossRefGoogle Scholar
  4. 4.
    Panagopoulos I, Micci F, Thorsen J, Gorunova L, Eibak AM, Bjerkehagen B, Davidson B, Heim S (2012) Novel fusion of MYST/Esa1-associated factor 6 and PHF1 in endometrial stromal sarcoma. PLoS One 7:e39354CrossRefGoogle Scholar
  5. 5.
    Eryilmaz J, Pan P, Amaya MF, Allali-Hassani A, Dong A, Adams-Cioaba MA, MacKenzie F, Vedadi M, Min J (2009) Structural studies of a four-MBT repeat protein MBTD1. PLoS One 4:e7274CrossRefGoogle Scholar
  6. 6.
    Huynh KD, Fischle W, Verdin E, Bardwell VJ (2000) BCoR, a novel corepressor involved in BCL-6 repression. Genes Dev 14:1810–1823Google Scholar
  7. 7.
    Pagan JK, Arnold J, Hanchard KJ, Kumar R, Bruno T, Jones MJK, Richard DJ, Forrest A, Spurdle A, Verdin E, Crossley M, Fanciulli M, Chenevix-Trench G, Young DB, Khanna KK (2007) A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP. J Biol Chem 282:15248–15257CrossRefGoogle Scholar
  8. 8.
    Chiang S, Oliva E (2011) Cytogenetic and molecular aberrations in endometrial stromal tumors. Hum Pathol 42:609–617CrossRefGoogle Scholar
  9. 9.
    Ketel CS, Andersen EF, Vargas ML, Suh J, Strome S, Simon JA (2005) Subunit contributions to histone methyltransferase activities of fly and worm polycomb group complexes. Mol Cell Biol 25:6857–6868CrossRefGoogle Scholar
  10. 10.
    Ma X, Wang J, Ma CX, Gao X, Patriub V, Sklar JL (2017) The JAZF1-SUZ12 fusion protein disrupts PRC2 complexes and impairs chromatin repression during human endometrial stromal tumorogenesis. Oncotarget 8:4062–4078Google Scholar
  11. 11.
    Li H, Ma X, Wang J, Koontz J, Nucci M, Sklar J (2007) Effects of rearrangement and allelic exclusion of JJAZ1/SUZ12 on cell proliferation and survival. Proc Natl Acad Sci U S A 104:20001–20006CrossRefGoogle Scholar
  12. 12.
    Avvakumov N, Cote J (2007) The MYST family of histone acetyltransferases and their intimate links to cancer. Oncogene 26:5395–5407CrossRefGoogle Scholar
  13. 13.
    He L, Li JD, Xiong Y, Huang X, Huang L, Lin JX, Zhou Y, Zheng M (2014) Clinicopathological and molecular markers associated with prognosis and treatment effectiveness of endometrial stromal sarcoma: a retrospective study in China. Arch Gynecol Obstet 289:383–391CrossRefGoogle Scholar
  14. 14.
    Rodgers SK, Kirby CL, Smith RJ, Horrow MM (2012) Imaging after cesarean delivery: acute and chronic complications. Radiographics 32:1693–1712CrossRefGoogle Scholar
  15. 15.
    Antonescu CR, Sung YS, Chen CL, Zhang L, Chen HW, Singer S, Agaram NP, Sboner A, Fletcher CD (2014) Novel ZC3H7B-BCOR, MEAF6-PHF1, and EPC1-PHF1 fusions in ossifying fibromyxoid tumors--molecular characterization shows genetic overlap with endometrial stromal sarcoma. Genes Chromosom Cancer 53:183–193CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Naohiro Makise
    • 1
    • 2
  • Masaya Sekimizu
    • 3
  • Eisuke Kobayashi
    • 4
    • 5
  • Hiroshi Yoshida
    • 1
  • Masashi Fukayama
    • 2
  • Tomoyasu Kato
    • 5
    • 6
  • Akira Kawai
    • 4
    • 5
  • Hitoshi Ichikawa
    • 3
    • 7
  • Akihiko Yoshida
    • 1
    • 5
    Email author
  1. 1.Department of Pathology and Clinical LaboratoriesNational Cancer Center HospitalTokyoJapan
  2. 2.Department of Pathologythe University of TokyoTokyoJapan
  3. 3.Department of Clinical GenomicsNational Cancer Center Research InstituteTokyoJapan
  4. 4.Department of Musculoskeletal OncologyNational Cancer Center HospitalTokyoJapan
  5. 5.Rare Cancer CenterNational Cancer Center HospitalTokyoJapan
  6. 6.Department of Gynecologic OncologyNational Cancer Center HospitalTokyoJapan
  7. 7.Division of Translational Genomics, Exploratory Oncology Research and Clinical Trial CenterNational Cancer CenterTokyoJapan

Personalised recommendations