Skip to main content

Advertisement

SpringerLink
Log in

High-grade neuroepithelial tumor with EP300::BCOR fusion and negative BCOR immunohistochemical expression: a case report

  • Case Report
  • Published:
Brain Tumor Pathology Aims and scope Submit manuscript

Abstract

In the World Health Organization tumor classification (fifth edition), central nervous system (CNS) tumors with BCOR internal tandem duplications have been recognized as a new tumor type. Some recent studies have reported CNS tumors with EP300::BCOR fusions, predominantly in children and young adults, expanding the spectrum of BCOR-altered CNS tumors. This study reports a new case of high-grade neuroepithelial tumor (HGNET) with an EP300::BCOR fusion in the occipital lobe of a 32-year-old female. The tumor displayed anaplastic ependymoma-like morphologies characterized by a relatively well-circumscribed solid growth with perivascular pseudorosettes and branching capillaries. Immunohistochemically, OLIG2 was focally positive and BCOR was negative. RNA sequencing revealed an EP300::BCOR fusion. The Deutsches Krebsforschungszentrum DNA methylation classifier (v12.5) classified the tumor as CNS tumor with BCOR/BCORL1 fusion. The t-distributed stochastic neighbor embedding analysis plotted the tumor close to the HGNET with BCOR alteration reference samples. BCOR/BCORL1-altered tumors should be included in the differential diagnosis of supratentorial CNS tumors with ependymoma-like histological features, especially when they lack ZFTA fusion or express OLIG2 even in the absence of BCOR expression. Analysis of published CNS tumors with BCOR/BCORL1 fusions revealed partly overlapping but not identical phenotypes. Further studies of additional cases are required to establish their classification.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Huynh KD, Fischle W, Verdin E et al (2000) BCoR, a novel corepressor involved in BCL-6 repression. Genes Dev 14:1810–1823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Blackledge NP, Rose NR, Klose RJ (2015) Targeting Polycomb systems to regulate gene expression: modifications to a complex story. Nat Rev Mol Cell Biol 16:643–649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Pierron G, Tirode F, Lucchesi C et al (2012) A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion. Nat Genet 44:461–466

    Article  CAS  PubMed  Google Scholar 

  4. Specht K, Zhang L, Sung YS et al (2016) Novel BCOR-MAML3 and ZC3H7B-BCOR gene fusions in undifferentiated small blue round cell sarcomas. Am J Surg Pathol 40:433–442

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kao YC, Owosho AA, Sung YS et al (2018) BCOR-CCNB3 fusion positive sarcomas: a clinicopathologic and molecular analysis of 36 cases with comparison to morphologic spectrum and clinical behavior of other round cell sarcomas. Am J Surg Pathol 42:604–615

    Article  PubMed  PubMed Central  Google Scholar 

  6. Yoshida A, Arai Y, Hama N et al (2020) Expanding the clinicopathologic and molecular spectrum of BCOR-associated sarcomas in adults. Histopathology 76:509–520

    Article  PubMed  Google Scholar 

  7. Kao YC, Sung YS, Zhang L et al (2016) Recurrent BCOR internal tandem duplication and YWHAE-NUTM2B fusions in soft tissue undifferentiated round cell sarcoma of infancy: overlapping genetic features with clear cell sarcoma of kidney. Am J Surg Pathol 40:1009–1020

    Article  PubMed  PubMed Central  Google Scholar 

  8. Roy A, Kumar V, Zorman B et al (2015) Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nat Commun 6:8891

    Article  CAS  PubMed  Google Scholar 

  9. Ueno-Yokohata H, Okita H, Nakasato K et al (2015) Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney. Nat Genet 47:861–863

    Article  CAS  PubMed  Google Scholar 

  10. 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 31:674–684

    Article  PubMed  Google Scholar 

  11. Marino-Enriquez A, Lauria A, Przybyl J et al (2018) BCOR internal tandem duplication in high-grade uterine sarcomas. Am J Surg Pathol 42:335–341

    Article  PubMed  Google Scholar 

  12. 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 30:1251–1261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Koelsche C, Schrimpf D, Stichel D et al (2021) Sarcoma classification by DNA methylation profiling. Nat Commun 12:498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sturm D, Orr BA, Toprak UH et al (2016) New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell 164:1060–1072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. WHO Classification of Tumours Editorial Board (2021) WHO Classification of Tumours, Central nervous system tumours, 5th ed. International Agency for Research on Cancer World Health Organization, Lyon

  16. Appay R, Macagno N, Padovani L et al (2017) HGNET-BCOR tumors of the cerebellum: clinicopathologic and molecular characterization of 3 cases. Am J Surg Pathol 41:1254–1260

    Article  PubMed  Google Scholar 

  17. Kline CN, Joseph NM, Grenert JP et al (2017) Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy. Neuro Oncol 19:699–709

    CAS  PubMed  Google Scholar 

  18. Yoshida Y, Nobusawa S, Nakata S et al (2018) CNS high-grade neuroepithelial tumor with BCOR internal tandem duplication: a comparison with its counterparts in the kidney and soft tissue. Brain Pathol 28:710–720

    Article  CAS  PubMed  Google Scholar 

  19. Fukuoka K, Kanemura Y, Shofuda T et al (2018) Significance of molecular classification of ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are a heterogeneous group of tumors. Acta Neuropathol Commun 6:134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yamazaki A, Arai Y, Fukuoka K et al (2022) Diffusely infiltrating glioma with CREBBP-BCORL1 fusion showing overexpression of not only BCORL1 but BCOR: a case report. Brain Tumor Pathol 39:171–178

    Article  CAS  PubMed  Google Scholar 

  21. Torre M, Meredith DM, Dubuc A et al (2019) Recurrent EP300-BCOR fusions in pediatric gliomas with distinct clinicopathologic features. J Neuropathol Exp Neurol 78:305–314

    Article  CAS  PubMed  Google Scholar 

  22. Tauziède-Espariat A, Pierron G, Siegfried A et al (2020) The EP300:BCOR fusion extends the genetic alteration spectrum defining the new tumoral entity of “CNS tumors with BCOR internal tandem duplication.” Acta Neuropathol Commun 8:178

    Article  PubMed  PubMed Central  Google Scholar 

  23. Wu Z, Rajan S, Chung HJ et al (2022) Molecular and clinicopathologic characteristics of gliomas with EP300::BCOR fusions. Acta Neuropathol 144:1175–1178

    Article  CAS  PubMed  Google Scholar 

  24. Capper D, Jones DTW, Sill M et al (2018) DNA methylation-based classification of central nervous system tumours. Nature 555:469–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pisapia DJ, Ohara K, Bareja R et al (2020) Fusions involving BCOR and CREBBP are rare events in infiltrating glioma. Acta Neuropathol Commun 8:80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors acknowledge Eijitsu Ryo, Ph.D., for the technical assistance. This work was partly supported by JSPS KAKENHI (Grant Number JP21K06919, AY) and the Rare Cancer Grant (G007, AY).

Author information

Authors and Affiliations

  1. Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Hirokazu Sugino, Kaishi Satomi, Taisuke Mori & Akihiko Yoshida

  2. Department of Pathology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan

    Kaishi Satomi

  3. Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Yuuki Mukai, Mai Honda-Kitahara & Yoshitaka Narita

  4. Department of Brain Disease Translational Research, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan

    Yuko Matsushita & Koichi Ichimura

  5. Rare Cancer Center, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Yoshitaka Narita & Akihiko Yoshida

Authors
  1. Hirokazu Sugino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kaishi Satomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taisuke Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuuki Mukai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mai Honda-Kitahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuko Matsushita
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Koichi Ichimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yoshitaka Narita
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Akihiko Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YMu and YN collected the clinical samples and generated the data. HS, KS, and AY performed histological analyses. TM, KS, MH-K, YMa, and KI generated, analyzed, and interpreted the molecular data. HS and AY prepared the manuscript with contributions from all authors.

Corresponding author

Correspondence to Akihiko Yoshida.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

This study was approved by the Institutional Review Board of the National Cancer Center Hospital, Tokyo, Japan (No. 2019-297).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 17 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sugino, H., Satomi, K., Mori, T. et al. High-grade neuroepithelial tumor with EP300::BCOR fusion and negative BCOR immunohistochemical expression: a case report. Brain Tumor Pathol 40, 133–141 (2023). https://doi.org/10.1007/s10014-023-00451-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10014-023-00451-y

Keywords

Search

Navigation