Supratentorial neuroepithelial tumor with PLAGL1 gene fusion — a new type of morphologically variable pediatric brain neoplasm defined by a distinct DNA methylation class. A case report and literature review

Kopachev D.N.; Ryzhova M.V.; Kislyakov A.N.; Shaikhaev E.G.; Zheludkova O.G.; Kumirova E.V.; Meshcheryakov S.V.; Vlasov P.A.; Shkatova A.M.; Semenova Zh.B.; Gushcha A.O.

doi:https://doi.org/10.17116/neiro20248802162

Kopachev D.N.

Research Institute for Emergency Pediatric Surgery and Traumatology;
Neurology Research Center

ORCID: 0000-0002-5501-9062

Ryzhova M.V.

Burdenko Neurosurgical Center

ORCID: 0000-0001-7206-6365

Kislyakov A.N.

Morozov Children’s Clinical Hospital

ORCID: 0000-0001-8735-4909

Shaikhaev E.G.

Burdenko Neurosurgical Center

ORCID: 0000-0002-7882-2579

Zheludkova O.G.

Voyno-Yasenetsky Practical Center for Specialized Medical Care for Children

ORCID: 0000-0002-8607-3635

Kumirova E.V.

Morozov Children’s Clinical Hospital

ORCID: 0000-0001-6125-2410

Meshcheryakov S.V.

Research Institute for Emergency Pediatric Surgery and Traumatology

ORCID: 0000-0003-3701-4628

Vlasov P.A.

Burdenko Neurosurgical Center

ORCID: 0000-0003-2381-8609

Shkatova A.M.

Burdenko Neurosurgical Center

ORCID: 0000-0003-4957-4286

Semenova Zh.B.

Research Institute for Emergency Pediatric Surgery and Traumatology

ORCID: 0000-0002-2018-050X

Gushcha A.O.

Neurology Research Center

ORCID: 0000-0003-3451-5750

Supratentorial neuroepithelial tumor with PLAGL1 gene fusion — a new type of morphologically variable pediatric brain neoplasm defined by a distinct DNA methylation class. A case report and literature review

Authors:

Kopachev D.N., Ryzhova M.V., Kislyakov A.N., Shaikhaev E.G., Zheludkova O.G., Kumirova E.V., Meshcheryakov S.V., Vlasov P.A., Shkatova A.M., Semenova Zh.B., Gushcha A.O.

More about the authors

Journal: Burdenko's Journal of Neurosurgery. 2024;88(2): 62‑68

DOI: 10.17116/neiro20248802162

Read: 2346 times

To cite this article:

Kopachev DN, Ryzhova MV, Kislyakov AN, et al. . Supratentorial neuroepithelial tumor with PLAGL1 gene fusion — a new type of morphologically variable pediatric brain neoplasm defined by a distinct DNA methylation class. A case report and literature review. Burdenko's Journal of Neurosurgery. 2024;88(2):62‑68. (In Russ., In Engl.)
https://doi.org/10.17116/neiro20248802162

Подписка 2025 Журнал «Вопросы нейрохирургии» имени Н.Н. Бурденко (Burdenko's Journal of Neurosurgery)

Использование инфографики авторами научных работ

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BACKGROUND

Methylation analysis has become a powerful diagnostic tool in modern neurooncology. This technique is valuable to diagnose new brain tumor types.

OBJECTIVE

To describe the MRI and histological pattern of neuroepithelial tumor with PLAGL1 gene fusion.

MATERIAL AND METHODS

We present a 6-year-old patient with small right frontal intraaxial tumor causing drug resistant epilepsy. Despite indolent preoperative clinical course and MRI features suggesting glioneuronal tumor, histological evaluation revealed characteristics of high-grade glioma, ependymoma and neuroblastoma.

RESULTS

Methylation analysis of tumor DNA confirmed a new type of a recently discovered neoplasm — neuroepithelial tumor with PLAGL1 fusion (NET PLAGL1). PCR confirmed fusion of PLAGL1 and EWSR1 genes. No seizures were observed throughout the follow-up period. There was no tumor relapse a year after surgery.

CONCLUSION

Methylation analysis in neurooncology is essential for unclear tumor morphology or divergence between histological and clinical data. In our case, this technique confirmed benign nature of tumor, and we preferred follow-up without unnecessary adjuvant treatment.

Keywords:

PLAG1

methylation analysis

neurooncology

glioneuronal tumor

Authors:

Kopachev D.N.

Research Institute for Emergency Pediatric Surgery and Traumatology;
Neurology Research Center

ORCID: 0000-0002-5501-9062

Ryzhova M.V.

Burdenko Neurosurgical Center

ORCID: 0000-0001-7206-6365

Kislyakov A.N.

Morozov Children’s Clinical Hospital

ORCID: 0000-0001-8735-4909

Shaikhaev E.G.

Burdenko Neurosurgical Center

ORCID: 0000-0002-7882-2579

Zheludkova O.G.

Voyno-Yasenetsky Practical Center for Specialized Medical Care for Children

ORCID: 0000-0002-8607-3635

Kumirova E.V.

Morozov Children’s Clinical Hospital

ORCID: 0000-0001-6125-2410

Meshcheryakov S.V.

Research Institute for Emergency Pediatric Surgery and Traumatology

ORCID: 0000-0003-3701-4628

Vlasov P.A.

Burdenko Neurosurgical Center

ORCID: 0000-0003-2381-8609

Shkatova A.M.

Burdenko Neurosurgical Center

ORCID: 0000-0003-4957-4286

Semenova Zh.B.

Research Institute for Emergency Pediatric Surgery and Traumatology

ORCID: 0000-0002-2018-050X

Gushcha A.O.

Neurology Research Center

ORCID: 0000-0003-3451-5750

Received:

27.10.2023

Accepted:

12.01.2024

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References:

Ryzhova MV, Galstyan SA, Telysheva EN. Significance of DNA methylation assessment in the morphological diagnosis of brain tumours. Arkhiv Patologii. 2022;84(3):65-75. (In Russ.). https://doi.org/10.17116/patol20228403165
Sievers P, Henneken SC, Blume C, Sill M, Schrimpf D, Stichel D, Okonechnikov K, Reuss DE, Benzel J, Maaß KK, Kool M, Sturm D, Zheng T, Ghasemi DR, Kohlhof-Meinecke P, Cruz O, Suñol M, Lavarino C, Ruf V, Boldt HB, Pagès M, Pouget C, Schweizer L, Kranendonk MEG, Akhtar N, Bunkowski S, Stadelmann C, Schüller U, Mueller WC, Dohmen H, Acker T, Harter PN, Mawrin C, Beschorner R, Brandner S, Snuderl M, Abdullaev Z, Aldape K, Gilbert MR, Armstrong TS, Ellison DW, Capper D, Ichimura K, Reifenberger G, Grundy RG, Jabado N, Krskova L, Zapotocky M, Vicha A, Varlet P, Wesseling P, Rutkowski S, Korshunov A, Wick W, Pfister SM, Jones DTW, von Deimling A, Pajtler KW, Sahm F. Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors. Acta neuropathologica. 2021;142(5):827-839. https://doi.org/10.1007/s00401-021-02356-6
Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, Kratz A, Wefers AK, Huang K, Pajtler KW, Schweizer L, Stichel D, Olar A, Engel NW, Lindenberg K, Harter PN, Braczynski AK, Plate KH, Dohmen H, Garvalov BK, Coras R, Hölsken A, Hewer E, Bewerunge-Hudler M, Schick M, Fischer R, Beschorner R, Schittenhelm J, Staszewski O, Wani K, Varlet P, Pages M, Temming P, Lohmann D, Selt F, Witt H, Milde T, Witt O, Aronica E, Giangaspero F, Rushing E, Scheurlen W, Geisenberger C, Rodriguez FJ, Becker A, Preusser M, Haberler C, Bjerkvig R, Cryan J, Farrell M, Deckert M, Hench J, Frank S, Serrano J, Kannan K, Tsirigos A, Brück W, Hofer S, Brehmer S, Seiz-Rosenhagen M, Hänggi D, Hans V, Rozsnoki S, Hansford JR, Kohlhof P, Kristensen BW, Lechner M, Lopes B, Mawrin C, Ketter R, Kulozik A, Khatib Z, Heppner F, Koch A, Jouvet A, Keohane C, Mühleisen H, Mueller W, Pohl U, Prinz M, Benner A, Zapatka M, Gottardo NG, Driever PH, Kramm CM, Müller HL, Rutkowski S, von Hoff K, Frühwald MC, Gnekow A, Fleischhack G, Tippelt S, Calaminus G, Monoranu CM, Perry A, Jones C, Jacques TS, Radlwimmer B, Gessi M, Pietsch T, Schramm J, Schackert G, Westphal M, Reifenberger G, Wesseling P, Weller M, Collins VP, Blümcke I, Bendszus M, Debus J, Huang A, Jabado N, Northcott PA, Paulus W, Gajjar A, Robinson GW, Taylor MD, Jaunmuktane Z, Ryzhova M, Platten M, Unterberg A, Wick W, Karajannis MA, Mittelbronn M, Acker T, Hartmann C, Aldape K, Schüller U, Buslei R, Lichter P, Kool M, Herold-Mende C, Ellison DW, Hasselblatt M, Snuderl M, Brandner S, Korshunov A, von Deimling A, Pfister SM. DNA methylation-based classification of central nervous system tumours. Nature. 2018;555(7697):469-474. https://doi.org/10.1038/nature26000
Koelsche C, von Deimling A. Methylation classifiers: Brain tumors, sarcomas, and what’s next. Genes, chromosomes & cancer. 2022;61(6):346-355. https://doi.org/10.1002/gcc.23041
Simsek O, Viaene AN, Andronikou S. Imaging in a new pediatric brain tumor-a supratentorial neuroepithelial tumor with PLAGL1 fusion. Child’s nervous system. 2023;39(6):1653-1656. https://doi.org/10.1007/s00381-023-05830-6
Lopez-Nunez O, Cafferata B, Santi M, Ranganathan S, Pearce TM, Kulich SM, Bailey KM, Broniscer A, Rossi S, Zin A, Nasrallah MP, Li MM, Zhong Y, Miele E, Alaggio R, Surrey LF. The spectrum of rare central nervous system (CNS) tumors with EWSR1-non-ETS fusions: experience from three pediatric institutions with review of the literature. Brain pathology. 2021;31(1):70-83. https://doi.org/10.1111/bpa.12900
Xing AY, Yang WW, Liu YL, Sun NN, Hao XM, Wang SX, Mu K. Rare Recurrent EWSR1-PLAGL1 Rearranged Intracranial Tumor With Biphasic Epithelioid Differentiation: One Case Report With Literature Review. Frontiers in oncology. 2022;12:938385. https://doi.org/10.3389/fonc.2022.938385
Keck MK, Sill M, Wittmann A, Joshi P, Stichel D, Beck P, Okonechnikow K, Sievers P, Wefers AK, Roncaroli F, Avula S, McCabe MG, Hayden JT, Wesseling P, Øra I, Nistér M, Kranendonk MEG, Tops BBJ, Zapotocky M, Zamecnik J, Vasiljevic A, Fenouil T, Meyronet D, von Hoff K, Schüller U, Loiseau H, Figarella-Branger D, Kramm CM, Sturm D, Scheie D, Rauramaa T, Pesola J, Gojo J, Haberler C, Brandner S, Jacques T, Sexton Oates A, Saffery R, Koscielniak E, Baker SJ, Yip S, Snuderl M, Ud Din N, Samuel D, Schramm K, Blattner-Johnson M, Selt F, Ecker J, Milde T, von Deimling A, Korshunov A, Perry A, Pfister SM, Sahm F, Solomon DA, Jones DTW. Amplification of the PLAG-family genes-PLAGL1 and PLAGL2-is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification. Acta neuropathologica. 2023;145(1):49-69. https://doi.org/10.1007/s00401-022-02516-2
Kopachev DN, Shishkina LV, Shkatova AM, Golovteev AL, Troitsky AA, Grinenko OA, Sharkova SM, Petrosyan DV, Gushcha AO. Long-term epilepsy-associated tumors. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2022;122(4):127-134. (In Russ.). https://doi.org/10.17116/jnevro2022122041127
Karimi S, Zuccato JA, Mamatjan Y, Mansouri S, Suppiah S, Nassiri F, Diamandis P, Munoz DG, Aldape KD, Zadeh G. The central nervous system tumor methylation classifier changes neuro-oncology practice for challenging brain tumor diagnoses and directly impacts patient care. Clinical epigenetics. 2019;11(1):185. https://doi.org/10.1186/s13148-019-0766-2