Gliomas and glioneuronal tumors in children. Interpretation of molecular features

This review consolidates current knowledge on genetic alterations observed in pediatric glial and glioneuronal tumors of the central nervous system (CNS). Some of these alterations serve as diagnostic biomarkers, whereas others may inform the selection of targeted therapeutic strategies. Drawing on both diagnostic and clinical perspectives, the authors aim to facilitate a more comprehensive understanding of the WHO Classification of CNS Tumors and to promote interdisciplinary collaboration. This resource is intended to support accurate tumor classification, guide molecular testing, and aid in identifying actionable genetic targets. The content may be of practical value to pediatric neuro-oncologists, molecular pathologists, neuropathologists, and researchers involved in CNS tumor diagnostics and treatment. For user convenience, selected data are summarized in tables.

1. Siegel B.I., Duke E.S., Kilburn L.B., Packer R.J. Molecular-targeted therapy for childhood low-grade glial and glioneuronal tumors. Childs Nerv Syst. 2024;40(10):3251–62. doi: 10.1007/s00381-024-06486-6. Epub 2024 Jun 15. PMID: 38877124.

2. Capper D., Reifenberger G., French P.J., Schweizer L., Weller M., Touat M., Niclou S.P., Euskirchen P., Haberler C., Hegi M.E., Brandner S., Le Rhun E., Rudà R., Sanson M., Tabatabai G., Sahm F., Wen P.Y., Wesseling P., Preusser M., van den Bent M.J. EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection. Neuro Oncol. 2023;25(5):813–26. doi: 10.1093/neuonc/noad008. PMID: 36632791; PMCID: PMC10158123.

3. Louis D.N., Perry A., Wesseling P., Brat D.J., Cree I.A., FigarellaBranger D., Hawkins C., Ng H.K., Pfi ster S.M., Reifenberger G., Soffi etti R., von Deimling A., Ellison D.W. The 2021 WHO classifi cation of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23(8):1231–51. doi: 10.1093/neuonc/noab106. PMID: 34185076; PMCID: PMC8328013.

4. Horbinski C., Berger T., Packer R.J., Wen P.Y. Clinical implications of the 2021 edition of the WHO classifi cation of central nervous system tumours. Nat Rev Neurol. 2022;18(9):515–29. doi: 10.1038/s41582-022-00679-w. Epub 2022 Jun 21. PMID: 35729337.

5. d'Amati A., Bargiacchi L., Rossi S., Carai A., Bertero L., Barresi V., Errico M.E., Buccoliero A.M., Asioli S., Marucci G., Del Baldo G., Mastronuzzi A., Miele E., D'Antonio F., Schiavello E., Biassoni V., Massimino M., Gessi M., Antonelli M., Gianno F. Pediatric CNS tumors and 2021 WHO classifi cation: what do oncologists need from pathologists? Front Mol Neurosci. 2024;17:1268038. doi: 10.3389/fnmol.2024.1268038. Erratum in: Front Mol Neurosci. 2024;17:1411360. doi: 10.3389/fnmol.2024.1411360. PMID: 38544524; PMCID: PMC10966132.

6. Lassaletta A., Zapotocky M., Mistry M., Ramaswamy V., Honnorat M., Krishnatry R., Guerreiro Stucklin A., Zhukova N., Arnoldo A., Ryall S., Ling C., McKeown T., Loukides J., Cruz O., de Torres C., Ho C.Y., Packer R.J., Tatevossian R., Qaddoumi I., Harreld J.H., Dalton J.D., Mulcahy-Levy J., Foreman N., Karajannis M.A., Wang S., Snuderl M., Nageswara Rao A., Giannini C., Kieran M., Ligon K.L., Garre M.L., Nozza P., Mascelli S., Raso A., Mueller S., Nicolaides T., Silva K., Perbet R., Vasiljevic A., Faure Conter C., Frappaz D., Leary S., Crane C., Chan A., Ng H.K., Shi Z.F., Mao Y., Finch E., Eisenstat D., Wilson B., Carret A.S., Hauser P., Sumerauer D., Krskova L., Larouche V., Fleming A., Zelcer S., Jabado N., Rutka J.T., Dirks P., Taylor M.D., Chen S., Bartels U., Huang A., Ellison D.W., Bouff et E., Hawkins C., Tabori U. Therapeutic and prognostic implications of BRAF V600E in Pediatric low-grade gliomas. J Clin Oncol. 2017;35(25):2934–41. doi: 10.1200/JCO.2016.71.8726. Epub 2017 Jul 20. PMID: 28727518; PMCID: PMC5791837.

7. Ryzhova M.V., Shaikhaev E.G., Snigireva G.P., Gorelyshev S.K., Zheludkova O.G., Golanov A.V. Novel BRAF::EPB41L2 gene fusion in posterior fossa pilocytic astrocytoma. Brief communication. Arkhiv patologii = Pathology Archive. 2022;84(5):40–2. (In Russ.).

8. Cloutier J.M., Al-Rohil R.N., Patel R.M., Ko J.S., Linos K. Ancillary tools for the diagnosis of CIC-rearranged sarcoma: a comprehensive review. J Cutan Pathol. 2025;52(4):324–31. doi: 10.1111/cup.14792. Epub 2025 Feb 8. PMID: 39921488.

9. Schwalbe E.C., Lindsey J.C., Danilenko M., Hill R.M., Crosier S., Ryan S.L., Williamson D., Castle J., Hicks D., Kool M., Milde T., Korshunov A., Pfi ster S.M., Bailey S., Cliff ord S.C. Molecular and clinical heterogeneity within MYC-family amplifi ed medulloblastoma is associated with survival outcomes: a multicenter cohort study. Neuro Oncol. 2025;27(1):222–36. doi: 10.1093/neuonc/noae178. PMID: 39377358; PMCID: PMC11726341.

10. Ryzhova M.V., Galstyan S.A., Telysheva E.N. Signifi cance of DNA methylation assessment in the morphological diagnosis of brain tumours. Arkhiv patologii = Pathology Archive. 2022;84(3):65–75. (In Russ.).

11. Capper D., Stichel D., Sahm F., Jones D.T.W., Schrimpf D., Sill M., Schmid S., Hovestadt V., Reuss D.E., Koelsche C., Reinhardt A., Wefers A.K., Huang K., Sievers P., Ebrahimi A., Schöler A., Teichmann D., Koch A., Hänggi D., Unterberg A., Platten M., Wick W., Witt O., Milde T., Korshunov A., Pfi ster S.M., von Deimling A. Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. Acta Neuropathol. 2018;136(2):181–210. doi: 10.1007/s00401-018-1879-y. Epub 2018 Jul 2. PMID: 29967940; PMCID: PMC6060790.

12. Alhalabi K.T., Stichel D., Sievers P., Peterziel H., Sommerkamp A.C., Sturm D., Wittmann A., Sill M., Jäger N., Beck P., Pajtler K.W., Snuderl M., Jour G., Delorenzo M., Martin A.M., Levy A., Dalvi N., Hansford J.R., Gottardo N.G., Uro-Coste E., Maurage C.A., Godfraind C., Vandenbos F., Pietsch T., Kramm C., Filippidou M., Kattamis A., Jones C., Øra I., Mikkelsen T.S., Zapotocky M., Sumerauer D., Scheie D., McCabe M., Wesseling P., Tops B.B.J., Kranendonk M.E.G., Karajannis M.A., Bouvier N., Papaemmanuil E., Dohmen H., Acker T., von Hoff K., Schmid S., Miele E., Filipski K., Kitanovski L., Krskova L., Gojo J., Haberler C., Alvaro F., Ecker J., Selt F., Milde T., Witt O., Oehme I., Kool M., von Deimling A., Korshunov A., Pfi ster S.M., Sahm F., Jones D.T.W. PATZ1 fusions defi ne a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum. Acta Neuropathol. 2021;142(5):841–57. doi: 10.1007/s00401-021-02354-8. Epub 2021 Aug 21. PMID: 34417833; PMCID: PMC8500868.

13. Sievers P., Henneken S.C., Blume C., Sill M., Schrimpf D., Stichel D., Okonechnikov K., Reuss D.E., Benzel J., Maaß K.K., Kool M., Sturm D., Zheng T., Ghasemi D.R., Kohlhof-Meinecke P., Cruz O., Suñol M., Lavarino C., Ruf V., Boldt H.B., Pagès M., Pouget C., Schweizer L., Kranendonk M.E.G., Akhtar N., Bunkowski S., Stadelmann C., Schüller U., Mueller W.C., Dohmen H., Acker T., Harter P.N., Mawrin C., Beschorner R., Brandner S., Snuderl M., Abdullaev Z., Aldape K., Gilbert M.R., Armstrong T.S., Ellison D.W., Capper D., Ichimura K., Reifenberger G., Grundy R.G., Jabado N., Krskova L., Zapotocky M., Vicha A., Varlet P., Wesseling P., Rutkowski S., Korshunov A., Wick W., Pfi ster S.M., Jones D.T.W., von Deimling A., Pajtler K.W., Sahm F. Recurrent fusions in PLAGL1 defi ne a distinct subset of pediatric-type supratentorial neuroepithelial tumors. Acta Neuropathol. 2021;142(5):827–39. doi: 10.1007/s00401-021-02356-6. Epub 2021 Aug 5. PMID: 34355256; PMCID: PMC8500895.

14. Suwala A.K., Stichel D., Schrimpf D., Kloor M., Wefers A.K., Reinhardt A., Maas S.L.N., Kratz C.P., Schweizer L., Hasselblatt M., Snuderl M., Abedalthagafi M.S.J., Abdullaev Z., Monoranu C.M., Bergmann M., Pekrun A., Freyschlag C., Aronica E., Kramm C.M., Hinz F., Sievers P., Korshunov A., Kool M., Pfi ster S.M., Sturm D., Jones D.T.W., Wick W., Unterberg A., Hartmann C., Dodgshun A., Tabori U., Wesseling P., Sahm F., von Deimling A., Reuss D.E. Primary mismatch repair defi cient IDH-mutant astrocytoma (PMMRDIA) is a distinct type with a poor prognosis. Acta Neuropathol. 2021;141(1):85–100. doi: 10.1007/s00401-020-02243-6. Epub 2020 Nov 20. PMID: 33216206; PMCID: PMC7785563.

15. Keck M.K., Sill M., Wittmann A., Joshi P., Stichel D., Beck P., Okonechnikow K., Sievers P., Wefers A.K., Roncaroli F., Avula S., McCabe M.G., Hayden J.T., Wesseling P., Øra I., Nistér M., Kranendonk M.E.G., Tops B.B.J., Zapotocky M., Zamecnik J., Vasiljevic A., Fenouil T., Meyronet D., von Hoff K., Schüller U., Loiseau H., Figarella-Branger D., Kramm C.M., Sturm D., Scheie D., Rauramaa T., Pesola J., Gojo J., Haberler C., Brandner S., Jacques T., Sexton Oates A., Saff ery 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., Pfi ster S.M., Sahm F., Solomon D.A., Jones D.T.W. Amplifi cation of the PLAG-family genes-PLAGL1 and PLAGL2 – is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplifi cation. Acta Neuropathol. 2023;145(1):49–69. doi: 10.1007/s00401-022-02516-2. Epub 2022 Nov 27. Erratum in: Acta Neuropathol. 2023;145(4):511–4. doi: 10.1007/s00401-023-02538-4. PMID: 36437415; PMCID: PMC9807491.

16. Tauziède-Espariat A., Volodia-Dangouloff -Ros, Figarella-Branger D., Uro-Coste E., Nicaise Y., André N., Scavarda D., Testud B., Girard N., Rousseau A., Basset L., Chotard G., Jecko V., le Loarer F., Hostein I., Machet M.C., Tallegas M., Listrat A., Hasty L., Métais A., Chrétien F., Boddaert N., Varlet P.; RENOCLIP-LOC. Clinicopathological and molecular characterization of three cases classifi ed by DNA-methylation profi ling as “Glioneuronal Tumors, NOS, Subtype A”. Acta Neuropathol. 2022;144(6):1179–83. doi: 10.1007/s00401-022-02490-9. Epub 2022 Sep 19. PMID: 36121478.

17. Suwala A.K., Felix M., Friedel D., Stichel D., Schrimpf D., Hinz F., Hewer E., Schweizer L., Dohmen H., Pohl U., Staszewski O., Korshunov A., Stein M., Wongsurawat T., Cheunsuacchon P., Sathornsumetee S., Koelsche C., Turner C., Le Rhun E., Mühlebner A., Schucht P., Özduman K., Ono T., Shimizu H., Prinz M., Acker T., Herold-Mende C., Kessler T., Wick W., Capper D., Wesseling P., Sahm F., von Deimling A., Hartmann C., Reuss D.E. Oligosarcomas, IDH-mutant are distinct and aggressive. Acta Neuropathol. 2022;143(2):263–81. doi: 10.1007/s00401-021-02395-z. Epub 2021 Dec 30. PMID: 34967922; PMCID: PMC8742817.

18. Sievers P., Sill M., Schrimpf D., Friedel D., Sturm D., Gardberg M., Kurian K.M., Krskova L., Vicha A., Schaller T., Hagel C., Abdullaev Z., Aldape K., Jacques T.S., Korshunov A., Wick W., Pfi ster S.M., von Deimling A., Jones D.T.W., Sahm F. Epigenetic profi ling reveals a subset of pediatric-type glioneuronal tumors characterized by oncogenic gene fusions involving several targetable kinases. Acta Neuropathol. 2022;144(5):1049–52. doi: 10.1007/s00401-022-02492-7. Epub 2022 Sep 7. PMID: 36070143; PMCID: PMC9547789.

19. Lebrun L., Allard-Demoustiez S., Gilis N., van Campenhout C., Rodesch M., Roman C., Calò P., Lolli V., David P., Fricx C., De Witte O., Escande F., Maurage C.A., Salmon I. Clinicopathological and molecular characterization of a case classifi ed by DNA methylation profi ling as “CNS embryonal tumor with BRD4-LEUTX fusion”. Acta Neuropathol Commun. 2023;11(1):46. doi: 10.1186/ s40478-023-01549-2. PMID: 36934287; PMCID: PMC10024856.

20. Sievers P., Sill M., Schrimpf D., Abdullaev Z., Donson A.M., Lake J.A., Friedel D., Scheie D., Tynninen O., Rauramaa T., Vepsäläinen K.L., Samuel D., Chapman R., Grundy R.G., Pajtler K.W., Tauziède-Espariat A., Métais A., Varlet P., Snuderl M., Jacques T.S., Aldape K., Reuss D.E., Korshunov A., Wick W., Pfi ster S.M., von Deimling A., Sahm F., Jones D.T.W. Pediatric-type high-grade neuroepithelial tumors with CIC gene fusion share a common DNA methylation signature. NPJ Precis Oncol. 2023;7(1):30. doi: 10.1038/s41698-023-00372-1. PMID: 36964296; PMCID: PMC10039012.

21. Bogumil H., Sill M., Schrimpf D., Ismer B., Blume C., Rahmanzade R., Hinz F., Cherkezov A., Banan R., Friedel D., Reuss DE., Selt F., Ecker J., Milde T., Pajtler K.W., Schittenhelm J., Hench J., Frank S., Boldt H.B., Kristensen B.W., Scheie D., Melchior L.C., Olesen V., Sehested A., Boué D.R., Abdullaev Z., Satgunaseelan L., Kurth I., Seidlitz A., White C.L., Ng H.K., Shi Z.F., Haberler C., Deckert M., Timmer M., Goldbrunner R., Tauziède-Espariat A., Varlet P., Brandner S., Alexandrescu S., Snuderl M., Aldape K., Korshunov A., Witt O., Herold-Mende C., Unterberg A., Wick W., Pfi ster S.M., von Deimling A., Jones D.T.W., Sahm F., Sievers P. Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions. Acta Neuropathol. 2023;145(5):667–80. doi: 10.1007/s00401-023-02558-0. Epub 2023 Mar 18. PMID: 36933012; PMCID: PMC10119244.

22. Bouff et E., Hansford J.R., Garrè M.L., Hara J., Plant-Fox A., Aerts I., Locatelli F., van der Lugt J., Papusha L., Sahm F., Tabori U., Cohen K.J., Packer R.J., Witt O., Sandalic L., Bento Pereira da Silva A., Russo M., Hargrave D.R. Dabrafenib plus Trametinib in pediatric glioma with BRAF V600 mutations. N Engl J Med. 2023;389(12):1108–20. doi: 10.1056/NEJMoa2303815. PMID: 37733309.

23. Hargrave D.R., Bouff et E., Tabori U., Broniscer A., Cohen K.J., Hansford J.R., Geoerger B., Hingorani P., Dunkel I.J., Russo M.W., Tseng L., Dasgupta K., Gasal E., Whitlock J.A., Kieran M.W. Effi cacy and safety of dabrafenib in pediatric patients with BRAF V600 mutation-positive relapsed or refractory low-grade glioma: results from a phase I/IIa study. Clin Cancer Res. 2019;25(24):7303–11. doi: 10.1158/1078-0432.CCR-19-2177. PMID: 31811016.

24. Bouff et E., Geoerger B., Moertel C., Whitlock J.A., Aerts I., Hargrave D., Osterloh L., Tan E., Choi J., Russo M., Fox E. Effi cacy and safety of trametinib monotherapy or in combination with dabrafenib in pediatric BRAF V600-mutant low-grade glioma. J Clin Oncol. 2023;41(3):664–74. doi: 10.1200/JCO.22.01000. Epub 2022 Nov 14. PMID: 36375115; PMCID: PMC9870224.

25. Selt F., van Tilburg C.M., Bison B., Sievers P., Harting I., Ecker J., Pajtler K.W., Sahm F., Bahr A., Simon M., Jones D.T.W., Well L., Mautner V.F., Capper D., Hernáiz Driever P., Gnekow A., Pfi ster S.M., Witt O., Milde T. Response to trametinib treatment in progressive pediatric low-grade glioma patients. J Neurooncol. 2020;149(3):499–510. doi: 10.1007/s11060-020-03640-3. Epub 2020 Oct 7. PMID: 33026636; PMCID: PMC7609413.

26. Manoharan N., Choi J., Chordas C., Zimmerman M.A., Scully J., Clymer J., Filbin M., Ullrich N.J., Bandopadhayay P., Chi S.N., Yeo K.K. Trametinib for the treatment of recurrent/progressive pediatric low-grade glioma. J Neurooncol. 2020;149(2):253–62. doi: 10.1007/s11060-020-03592-8. Epub 2020 Aug 11. PMID: 32780261.

27. Paul M.R., Pehlivan K.C., Milburn M., Yeh-Nayre L., Elster J., Crawford J.R. Trametinib-based treatment of pediatric CNS tumors: a single institutional experience. J Pediatr Hematol Oncol. 2020;42(8):e730–7. doi: 10.1097/MPH.0000000000001819. PMID: 32398601.

28. Kondyli M., Larouche V., Saint-Martin C., Ellezam B., Pouliot L., Sinnett D., Legault G., Crevier L., Weil A., Farmer J.P., Jabado N., Perreault S. Trametinib for progressive pediatric low-grade gliomas. J Neurooncol. 2018;140(2):435–44. doi: 10.1007/s11060-018-2971-9. Epub 2018 Aug 10. PMID: 30097824.

29. Di Nunno V., Gatto L., Tosoni A., Bartolini S., Franceschi E. Implications of BRAF V600E mutation in gliomas: molecular considerations, prognostic value and treatment evolution. Front Oncol. 2023;12:1067252. doi: 10.3389/fonc.2022.1067252. PMID: 36686797; PMCID: PMC9846085.

30. Fangusaro J., Onar-Thomas A., Young Poussaint T., Wu S., Ligon A.H., Lindeman N., Banerjee A., Packer R.J., Kilburn L.B., Goldman S., Pollack I.F., Qaddoumi I., Jakacki R.I., Fisher P.G., Dhall G., Baxter P., Kreissman S.G., Stewart C.F., Jones D.T.W., Pfi ster S.M., Vezina G., Stern J.S., Panigrahy A., Patay Z., Tamrazi B., Jones J.Y., Haque S.S., Enterline D.S., Cha S., Fisher M.J., Doyle L.A., Smith M., Dunkel I.J., Fouladi M. Selumetinib in paediatric patients with BRAF-aberrant or neurofi bromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol. 2019;20(7):1011–22. doi: 10.1016/S1470-2045(19)30277-3. Epub 2019 May 28. PMID: 31151904; PMCID: PMC6628202.

31. Fangusaro J., Onar-Thomas A., Poussaint T.Y., Wu S., Ligon A.H., Lindeman N., Campagne O., Banerjee A., Gururangan S., Kilburn L.B., Goldman S., Qaddoumi I., Baxter P., Vezina G., Bregman C., Patay Z., Jones J.Y., Stewart C.F., Fisher M.J., Doyle LA, Smith M., Dunkel I.J., Fouladi M. A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study. Neuro Oncol. 2021;23(10):1777–88. doi: 10.1093/neuonc/noab047. PMID: 33631016; PMCID: PMC8485450.

32. van Tilburg C.M., Kilburn L.B., Perreault S., Schmidt R., Azizi A.A., Cruz-Martínez O., Zápotocký M., Scheinemann K., Meeteren A.Y.N.S., Sehested A., Opocher E., Driever P.H., Avula S., Ziegler D.S., Capper D., Koch A., Sahm F., Qiu J., Tsao L.P., Blackman S.C., Manley P., Milde T., Witt R., Jones D.T.W., Hargrave D., Witt O. LOGGIC/FIREFLY-2: a phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration. BMC Cancer. 2024;24(1):147. doi: 10.1186/s12885-024-11820-x. PMID: 38291372; PMCID: PMC10826080.

33. Armstrong A.E., Belzberg A.J., Crawford J.R., Hirbe A.C., Wang Z.J. Treatment decisions and the use of MEK inhibitors for children with neurofi bromatosis type 1-related plexiform neurofi bromas. BMC Cancer. 2023;23(1):553. doi: 10.1186/s12885-023-10996-y. PMID: 37328781; PMCID: PMC10273716.

34. Gibson E.G., Campagne O., Selvo N.S., Gajjar A., Stewart C.F. Population pharmacokinetic analysis of crizotinib in children with progressive/recurrent high-grade and diff use intrinsic pontine gliomas. Cancer Chemother Pharmacol. 2021;88(6):1009–20. doi: 10.1007/s00280-021-04357-4. Epub 2021 Sep 29. PMID: 34586478; PMCID: PMC8561710.

35. Stepien N., Mayr L., Schmook M.T., Raimann A., Dorfer C., Peyrl A., Azizi A.A., Schramm K., Haberler C., Gojo J. Feasibility and antitumour activity of the FGFR inhibitor erdafi tnib in three paediatric CNS tumour patients. Pediatr Blood Cancer. 2024;71(3):e30836. doi: 10.1002/pbc.30836. Epub 2024 Jan 4. PMID: 38177074.

36. Doz F., van Tilburg C.M., Geoerger B., Højgaard M., Øra I., Boni V., Capra M., Chisholm J., Chung H.C., DuBois S.G., Gallego-Melcon S., Gerber N.U., Goto H., Grilley-Olson J.E., Hansford J.R., Hong D.S., Italiano A., Kang H.J., Nysom K., Thorwarth A., Stefanowicz J., Tahara M., Ziegler D.S., Gavrilovic I.T., Norenberg R., Dima L., De La Cuesta E., Laetsch T.W., Drilon A., Perreault S. Effi cacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors. Neuro Oncol. 2022;24(6):997–1007. doi: 10.1093/neuonc/noab274. PMID: 34850167; PMCID: PMC9159442.

37. Simoneau J., Robertson P., Muraszko K., Maher C.O., Garton H., Calvert R., Koschmann C., Upadhyaya S.A., Mody R., Brown N., Kumar-Sinha C., Parmar H., Camelo-Piragua S., Franson A.T. Longterm tumor stability after fi rst-line treatment with larotrectinib in an infant with NTRK2 fusion-positive high-grade glioma. J Natl Compr Canc Netw. 2024;22(7):e247045. doi: 10.6004/jnccn.2024.7045. PMID: 39236755.

38. Cella E., Bosio A., Persico P., Caccese M., Padovan M., Losurdo A., Maccari M., Cerretti G., Ius T., Minniti G., Idbaih A., Sanai N., Weller M., Preusser M., Simonelli M., Lombardi G. PARP inhibitors in gliomas: mechanisms of action, current trends and future perspectives. Cancer Treat Rev. 2024;131:102850. doi: 10.1016/j.ctrv.2024.102850. Epub 2024 Nov 5. Erratum in: Cancer Treat Rev. 2025;132:102866. doi: 10.1016/j.ctrv.2024.102866. PMID: 39531943.

39. Cacciotti C., Fleming A., Ramaswamy V. Advances in the molecular classifi cation of pediatric brain tumors: a guide to the galaxy. J Pathol. 2020;251(3):249–61. doi: 10.1002/path.5457. Epub 2020 Jun 10. PMID: 32391583.

40. Ekhator C., Rak R., Tadipatri R., Fonkem E., Grewal J. A singlecenter experience of dopamine antagonist ONC201 for recurrent histone H3 lysine 27-to-methionine (H3K27M)-mutant glioblastoma in adults. Cureus. 2022;14(8):e28175. doi: 10.7759/cureus.28175. PMID: 36148206; PMCID: PMC9482800.

41. FDA approves fi rst IDH-targeted glioma drug. Nat Biotechnol. 2024;42:1325. doi: 10.1038/s41587-024-02408-8.

42. Tzaridis T., Wechsler-Reya R.J. Just a spoonful of metformin helps the medicine go down. J Clin Invest. 2024;134(6):e179144. doi: 10.1172/JCI179144. PMID: 38488006; PMCID: PMC10940077.

43. Luger A.L., König S., Samp P.F., Urban H., Divé I., Burger M.C., Voss M., Franz K., Fokas E., Filipski K., Demes M.C., Stenzinger A., Sahm F., Reuss D.E., Harter P.N., Wagner S., Hattingen E., Wichert J., Lapa C., Fröhling S., Steinbach J.P., Ronellenfi tsch M.W. Molecular matched targeted therapies for primary brain tumors – a single center retrospective analysis. J Neurooncol. 2022;159(2):243–59. doi: 10.1007/s11060-022-04049-w. Epub 2022 Jul 21. PMID: 35864412; PMCID: PMC9424147.