Tumor associated epilepsy and glioma: Are there any common genetics?

Patients with glioma demonstrate a high variability of clinical symptoms, in addition to differences in treatment response and survival. Many patients experience epileptic seizures at the onset of the disease, especially with low-grade gliomas, but not all have seizure episodes. A significant portion of patients develop refractory seizures. It is likely that the variability of epileptic symptoms cannot be explained solely by tumor-related factors, but rather reflects a complex interaction between tumor-related factors, environmental factors, and genetic factors.

MATERIALS AND METHODS. There is no data on predisposition genes associated with epileptic symptoms in patients with glioma. However, an increasing number of candidate genes have been proposed for other focal epilepsies, such as temporal lobe epilepsy. Some candidate genes associated with focal epilepsy may contribute to the development of epileptic symptoms in patients with glioma.

RESULTS. This review presents updated information on studies of genetic polymorphisms and focal epilepsy, as well as described candidate genes for tumor-associated epilepsy based on the assumption that there may be common etiological pathways for glioma development and glioma-associated seizures.

CONCLUSION. Genes involved in immune response, synaptic transmission, and cell cycle control are discussed as potential players in the pathogenesis of tumor growth and epileptic symptoms in patients with gliomas.

1. Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, Von Deimling A, Ellison DW. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231–1251. doi: 10.1093/neuonc/noab106. PMID: 34185076; PMCID: PMC 8328013.

2. Ohgaki, H., & Kleihues, P. (2005). Epidemiology and etiology of gliomas. Acta neuropathologica, 109(1), 93–108. https://doi.org/10.1007/s00401–005–0991-y

3. Schaff, L. R., & Mellinghoff, I. K. (2023). Glioblastoma and Other primary Brain Malignancies in Adults: A Review. JAMA, 329(7), 574–587. https://doi.org/10.1001/jama.2023.0023.

4. Stupp, R., Mason, W. P., Van Den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., Curschmann, J., Janzer, R. C., Ludwin, S. K., Gorlia, T., Allgeier, A., Lacombe, D., Cairncross, J. G., Eisenhauer, E., Mirimanoff, R. O. European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, … National Cancer Institute of Canada Clinical Trials Group (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. The New England journal of medicine, 352(10), 987–996. https://doi.org/10.1056/NEJMoa043330

5. Gusyatiner, O., & Hegi, M. E. (2018). Glioma epigenetics: From subclassification to novel treatment options. Seminars in cancer biology, 51, 50–58. https://doi.org/10.1016/j.semcancer.2017.11.010.

6. Xie, C., Xu, M., Lu, D., Zhang, W., Wang, L., Wang, H., Li, J., Ren, F., & Wang, C. (2018). Candidate genes and microRNAs for glioma pathogenesis and prognosis based on gene expression profiles. Molecular medicine reports, 18(3), 2715–2723. https://doi.org/10.3892/mmr.2018.9231

7. Brenner, A. V., Butler, M. A., Wang, S. S., Ruder, A. M., Rothman, N., Schulte, P. A., Chanock, S. J., Fine, H. A., Linet, M. S., & Inskip, P.D. (2007). Single-nucleotide polymorphisms in selected cytokine genes and risk of adult glioma. Carcinogenesis, 28(12), 2543–2547. https://doi.org/10.1093/carcin/bgm210

8. Rajaraman, P., Wang, S. S., Rothman, N., Brown, M. M., Black, P. M., Fine, H. A., Loeffler, J. S., Selker, R. G., Shapiro, W. R., Chanock, S. J., & Inskip, P. D. (2007). polymorphisms in apoptosis and cell cycle control genes and risk of brain tumors in adults. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of preventive Oncology, 16(8), 1655–1661. https://doi.org/10.1158/1055–9965.EpI-07–0314

9. Liu, Y., Scheurer, M. E., El-Zein, R., Cao, Y., Do, K. A., Gilbert, M., Aldape, K. D., Wei, Q., Etzel, C., & Bondy, M. L. (2009). Association and interactions between DNA repair gene polymorphisms and adult glioma. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of preventive Oncology, 18(1), 204–214. https://doi.org/10.1158/1055–9965.EpI-08–0632

10. Carpentier, C., Lejeune, J., Gros, F., Everhard, S., Marie, Y., Kaloshi, G., Laigle-Donadey, F., Hoang-Xuan, K., Delattre, J. Y., & Sanson, M. (2007). Association of telomerase gene hTERT polymorphism and malignant gliomas. Journal of neuro-oncology, 84(3), 249–253. https://doi.org/10.1007/s11060-007-9378-3.

11. Costa, B. M., Ferreira, P., Costa, S., Canedo, P., Oliveira, P., Silva, A., Pardal, F., Suriano, G., Machado, J. C., Lopes, J. M., & Reis, R. M. (2007). Association between functional EGF+61 polymorphism and glioma risk. Clinical cancer research: an official journal of the American Association for Cancer Research, 13(9), 2621–2626. https://doi.org/10.1158/1078–0432.CCR-06–2606

12. Lu, Z., Cao, Y., Wang, Y., Zhang, Q., Zhang, X., Wang, S., Li, Y., Xie, H., Jiao, B., & Zhang, J. (2007). polymorphisms in the matrix metalloproteinase-1, 3, and 9 promoters and susceptibility to adult astrocytoma in northern China. Journal of neuro-oncology, 85(1), 65–73. https://doi.org/10.1007/s11060-007-9392-5

13. Parhar, P., Ezer, R., Shao, Y., Allen, J. C., Miller, D. C., & Newcomb, E. W. (2005). possible association of p53 codon 72 polymorphism with susceptibility to adult and pediatric high-grade astrocytomas. Brain research. Molecular brain research, 137(1–2), 98–103. https://doi.org/10.1016/j.molbrainres.2005.02.016

14. Bhowmick, D. A., Zhuang, Z., Wait, S. D., & Weil, R. J. (2004). A functional polymorphism in the EGF gene is found with increased frequency in glioblastoma multiforme patients and is associated with more aggressive disease. Cancer research, 64(4), 1220–1223. https://doi.org/10.1158/0008–5472.can-03–3137

15. Coutinho, P., Sandim, V., Oliveira, J. A., Alves, G., & Hatagima, A. (2010). Lack of association between glutathione S-transferase polymorphisms and primary glioma in a case-control study in Rio de Janeiro. Genetics and molecular research: GMR, 9(1), 539–544. https://doi.org/10.4238/vol9–1gmr753

16. Wang, L. E., Bondy, M. L., Shen, H., El-Zein, R., Aldape, K., Cao, Y., Pudavalli, V., Levin, V. A., Yung, W. K., & Wei, Q. (2004). polymorphisms of DNA repair genes and risk of glioma. Cancer research, 64(16), 5560–5563. https://doi.org/10.1158/0008–5472.CAN-03–2181

17. Vastrad, B., Vastrad, C., Godavarthi, A., & Chandrashekar, R. (2017). Molecular mechanisms underlying gliomas and glioblastoma pathogenesis revealed by bioinformatics analysis of microarray data. Medical oncology (Northwood, London, England), 34(11), 182. https://doi.org/10.1007/s12032–017–1043-x

18. Bethke, L., Webb, E., Murray, A., Schoemaker, M., Johansen, C., Christensen, H. C., Muir, K., Mckinney, P., Hepworth, S., Dimitropoulou, P., Lophatananon, A., Feychting, M., Lönn, S., Ahlbom, A., Malmer, B., Henriksson, R., Auvinen, A., Kiuru, A., Salminen, T., Swerdlow, A., … Houlston, R. (2008). Comprehensive analysis of the role of DNA repair gene polymorphisms on risk of glioma. Human molecular genetics, 17(6), 800–805. https://doi.org/10.1093/hmg/ddm351

19. Jiang, Y., Wang, Z., Ying, C., Hu, J., Zeng, T., & Gao, L. (2021). FMR 1/circCHAF1A/miR-211–5p/HOXC 8 feedback loop regulates proliferation and tumorigenesis via MDM2-dependent p53 signaling in GSCs. Oncogene, 40(24), 4094–4110. https://doi.org/10.1038/s41388-021-01833-2.

20. Sun, G., Wang, X., Shi, L., Yue, X., Fu, L., Chen, C., Li, Z., Pan, T., & Wan, Z. (2013). Association between polymorphisms in interleukin-4Rα and interleukin-13 and glioma risk: a meta-analysis. Cancer epidemiology, 37(3), 306–310. https://doi.org/10.1016/j.canep.2013.01.003

21. Chen, P., Chen, C., Chen, K., Xu, T., & Luo, C. (2015). polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine, 36(1), 121–127. https://doi.org/10.1007/s13277-014-2895-8

22. Falco-Walter J. (2020). Epilepsy-definition, Classification, pathophysiology, and Epidemiology. Seminars in neurology, 40(6), 617–623. https://doi.org/10.1055/s-0040–1718719.

23. Fisher R. S. (2003). Retraction for misappropriation: brain tumor and seizures: pathophysiology and its implications for treatment revisited Bernhard Schaller and Stephan J. Rüegg Epilepsia 2003;44:1223–1232. Epilepsia, 44(11), 1463. https://doi.org/10.1046/j.1528–1157.2003.44114_1.x

24. Xu, D. S., Awad, A. W., Mehalechko, C., Wilson, J. R., Ashby, L. S., Coons, S. W., & Sanai, N. (2018). An extent of resection threshold for seizure freedom in patients with low-grade gliomas. Journal of neurosurgery, 128(4), 1084–1090. https://doi.org/10.3171/2016.12.JNS161682

25. Samudra, N., Zacharias, T., Plitt, A., Lega, B., & Pan, E. (2019). Seizures in glioma patients: An overview of incidence, etiology, and therapies. Journal of the neurological sciences, 404, 80–85. https://doi.org/10.1016/j.jns.2019.07.026

26. van Breemen, M. S., Wilms, E. B., & Vecht, C. J. (2007). Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. The Lancet. Neurology, 6(5), 421–430. https://doi.org/10.1016/S1474–4422(07)70103-5

27. Piepmeier, J., Christopher, S., Spencer, D., Byrne, T., Kim, J., Knisel, J. P., Lacy, J., Tsukerman, L., & Makuch, R. (1996). Variations in the natural history and survival of patients with supratentorial low-grade astrocytomas. Neurosurgery, 38(5), 872–879. https://doi.org/10.1097/00006123-199605000-00002

28. Kerkhof, M., & Vecht, C. J. (2013). Seizure characteristics and prognostic factors of gliomas. Epilepsia, 54 Suppl 9, 12–17. https://doi.org/10.1111/epi.12437

29. Kalachikov, S., Evgrafov, O., Ross, B., Winawer, M., Barker-Cummings, C., Martinelli Boneschi, F., Choi, C., Morozov, P., Das, K., Teplitskaya, E., Yu, A., Cayanis, E., Penchaszadeh, G., Kottmann, A. H., Pedley, T. A., Hauser, W. A., Ottman, R., & Gilliam, T. C. (2002). Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nature genetics, 30(3), 335–341. https://doi.org/10.1038/ng832

30. Lu, J., Zhao, G., Lv, D., Cao, L., & Zhao, G. (2022). Autosomal dominant sleep-related hypermotor epilepsy associated with a novel mutation of KCNT1. Translational neuroscience, 13(1), 240–245. https://doi.org/10.1515/tnsci-2022–0241

31. Mastrangelo, M., Salpietro, V., & Sullivan, J. (2022). Editorial: Genetically determined epilepsies: perspectives in the era of precision medicine. Frontiers in neurology, 13, 1036846. https://doi.org/10.3389/fneur.2022.1036846.

32. Cavalleri, G. L., Lynch, J. M., Depondt, C., Burley, M. W., Wood, N.W., Sisodiya, S. M., & Goldstein, D. B. (2005). Failure to replicate previously reported genetic associations with sporadic temporal lobe epilepsy: where to from here? Brain: a journal of neurology, 128(pt 8), 1832–1840. https://doi.org/10.1093/brain/awh524

33. Kanemoto, K., Kawasaki, J., Yuasa, S., Kumaki, T., Tomohiro, O., Kaji, R., & Nishimura, M. (2003). Increased frequency of interleukin-1beta-511T allele in patients with temporal lobe epilepsy, hippocampal sclerosis, and prolonged febrile convulsion. Epilepsia, 44(6), 796–799. https://doi.org/10.1046/j.1528–1157.2003.43302.x

34. Kanemoto, K., Kawasaki, J., Yuasa, S., Kumaki, T., Tomohiro, O., Kaji, R., & Nishimura, M. (2003). Increased frequency of interleukin-1beta-511T allele in patients with temporal lobe epilepsy, hippocampal sclerosis, and prolonged febrile convulsion. Epilepsia, 44(6), 796–799. https://doi.org/10.1046/j.1528–1157.2003.43302.x

35. Ozkara, C., Uzan, M., Tanriverdi, T., Baykara, O., Ekinci, B., Yeni, N., Kafadar, A., & Buyru, N. (2006). Lack of association between IL-1beta/alpha gene polymorphisms and temporal lobe epilepsy with hippocampal sclerosis. Seizure, 15(5), 288–291. https://doi.org/10.1016/j.seizure.2006.02.016.

36. Dundar, N. O., Aktekin, B., Ekinci, N. C., Sahinturk, D., Yavuzer, U., Yegin, O., & Haspolat, S. (2013). Interleukin-1β secretion in hippocampal sclerosis patients with mesial temporal lobe epilepsy. Neurology international, 5(3), e17. https://doi.org/10.4081/ni.2013.e17.

37. Buono, R. J., Ferraro, T. N., O’Connor, M. J., Sperling, M. R., Ryan, S. G., Scattergood, T., Mulholland, N., Gilmore, J., Lohoff, F.W., & Berrettini, W. H. (2001). Lack of association between an interleukin 1 beta (IL-1beta) gene variation and refractory temporal lobe epilepsy. Epilepsia, 42(6), 782–784. https://doi.org/10.1046/j.1528–1157.2001.42900.x.

38. Jin, L., Jia, Y., Zhang, B., Xu, Q., Fan, Y., Wu, L., & Shen, Y. (2003). Association analysis of a polymorphism of interleukin 1 beta (IL-1 beta) gene with temporal lobe epilepsy in a Chinese population. Epilepsia, 44(10), 1306–1309. https://doi.org/10.1046/j.1528–1157.2003.11003.x.

39. Gambardella, A., Manna, I., Labate, A., Chifari, R., La Russa, A., Serra, P., Cittadella, R., Bonavita, S., Andreoli, V., Lepiane, E., Sasanelli, F., Di Costanzo, A., Zappia, M., Tedeschi, G., Aguglia, U., & Quattrone, A. (2003). GABA(B) receptor 1 polymorphism (G1465A) is associated with temporal lobe epilepsy. Neurology, 60(4), 560–563. https://doi.org/10.1212/01.wnl.0000046520.79877.d8.

40. Ma, S., Abou-Khalil, B., Sutcliffe, J. S., Haines, J. L., & Hedera, P. (2005). The GABBR 1 locus and the G1465A variant is not associated with temporal lobe epilepsy preceded by febrile seizures. BMC medical genetics, 6, 13. https://doi.org/10.1186/1471-2350-6-13.

41. Ma, S., Abou-Khalil, B., Blair, M. A., Sutcliffe, J. S., Haines, J. L., & Hedera, P. (2006). Mutations in GABRA1, GABRA5, GABRG2 and GABRd receptor genes are not a major factor in the pathogenesis of familial focal epilepsy preceded by febrile seizures. Neuroscience letters, 394(1), 74–78. https://doi.org/10.1016/j.neulet.2005.10.006.

42. Manna, I., Labate, A., Gambardella, A., Forabosco, P., La Russa, A., Le Piane, E., Aguglia, U., & Quattrone, A. (2007). Serotonin transporter gene (5-Htt): association analysis with temporal lobe epilepsy. Neuroscience letters, 421(1), 52–56. https://doi.org/10.1016/j.neulet.2007.05.022.

43. Sporiš, D., Bašić, S., Sertić, J., Mahović Lakušić, D., & Babić, T. (2017). Is Apolipoprotein E ε2 Associated with delayed Onset of Non-Lesional Temporal Lobe Epilepsy?. Acta clinica Croatica, 56(1), 10–14. https://doi.org/10.20471/acc.2017.56.01.02.

44. Kukuruzović, M., Bašić Kes, V., & Malenica, M. (2021). ASSOCIATION between apolipoprotein E polymorphisms and epilepsy in children. Acta clinica Croatica, 60(4), 595–601. https://doi.org/10.20471/acc.2021.60.04.05.

45. Yeni, S. N., Ozkara, C., Buyru, N., Baykara, O., Hanoğlu, L., Karaağac, N., Ozyurt, E., & Uzan, M. (2005). Association between APOE polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis. European journal of neurology, 12(2), 103–107. https://doi.org/10.1111/j.1468–1331.2004.00956.x.

46. Briellmann, R. S., Torn-Broers, Y., Busuttil, B. E., Major, B. J., Kalnins, R. M., Olsen, M., Jackson, G. D., Frauman, A. G., & Berkovic, S. F. (2000). APOE epsilon4 genotype is associated with an earlier onset of chronic temporal lobe epilepsy. Neurology, 55(3), 435–437. https://doi.org/10.1212/wnl.55.3.435.

47. Kanemoto, K., Kawasaki, J., Tarao, Y., Kumaki, T., Oshima, T., Kaji, R., & Nishimura, M. (2003). Association of partial epilepsy with brain-derived neurotrophic factor (BDNF) gene polymorphisms. Epilepsy research, 53(3), 255–258. https://doi.org/10.1016/s0920–1211(03)00032-9.

48. Lohoff, F. W., Ferraro, T. N., Dahl, J. P., Hildebrandt, M. A., Scattergood, T. M., O’Connor, M. J., Sperling, M. R., Dlugos, D. J., Berrettini, W. H., & Buono, R. J. (2005). Lack of association between variations in the brain-derived neurotrophic factor (BdNF) gene and temporal lobe epilepsy. Epilepsy research, 66(1–3), 59–62. https://doi.org/10.1016/j.eplepsyres.2005.06.005.

49. Loacker, S., Sayyah, M., Wittmann, W., Herzog, H., & Schwarzer, C. (2007). Endogenous dynorphin in epileptogenesis and epilepsy: anticonvulsant net effect via kappa opioid receptors. Brain: a journal of neurology, 130(pt 4), 1017–1028. https://doi.org/10.1093/brain/awl384.

50. Stögmann, E., Zimprich, A., Baumgartner, C., Aull-Watschinger, S., Höllt, V., & Zimprich, F. (2002). A functional polymorphism in the prodynorphin gene promotor is associated with temporal lobe epilepsy. Annals of neurology, 51(2), 260–263. https://doi.org/10.1002/ana.10108.

51. Symonds, J. D., Zuberi, S. M., & Johnson, M. R. (2017). Advances in epilepsy gene discovery and implications for epilepsy diagnosis and treatment. Current opinion in neurology, 30(2), 193–199. https://doi.org/10.1097/WCO.0000000000000433.

52. Berntsson, S. G., Malmer, B., Bondy, M. L., Qu, M., & Smits, A. (2009). Tumor-associated epilepsy and glioma: are there common genetic pathways?. Acta oncologica (Stockholm, Sweden), 48(7), 955–963. https://doi.org/10.1080/02841860903104145.

53. Dai, L., & Shen, Y. (2021). Insights into T-cell dysfunction in Alzheimer’s disease. Aging cell, 20(12), e13511. https://doi.org/10.1111/acel.13511.

54. Avoli, M., & Lévesque, M. (2022). GABAB Receptors: are they Missing in Action in Focal Epilepsy Research?. Current neuropharmacology, 20(9), 1704–1716. https://doi.org/10.2174/1570159X19666210823102332.

55. Princivalle A. P. (2022). GABAB Receptors in Neurodegeneration. Current topics in behavioral neurosciences, 52, 267–290. https://doi.org/10.1007/7854_2021_222.

56. Mansouri, M., Kremser, L., Nguyen, T. P., Kasugai, Y., Caberlotto, L., Gassmann, M., Sarg, B., Lindner, H., Bettler, B., Carboni, L., & Ferraguti, F. (2023). protein Networks Associated with Native Metabotropic Glutamate 1 Receptors (mGlu1) in the Mouse Cerebellum. Cells, 12(9), 1325. https://doi.org/10.3390/cells12091325.

57. Xie, C., Xu, M., Lu, D., Zhang, W., Wang, L., Wang, H., Li, J., Ren, F., & Wang, C. (2018). Candidate genes and microRNAs for glioma pathogenesis and prognosis based on gene expression profiles. Molecular medicine reports, 18(3), 2715–2723. https://doi.org/10.3892/mmr.2018.9231.

58. Veenman, L., Levin, E., Weisinger, G., Leschiner, S., Spanier, I., Snyder, S. H., Weizman, A., & Gavish, M. (2004). peripheral-type benzodiazepine receptor density and in vitro tumorigenicity of glioma cell lines. Biochemical pharmacology, 68(4), 689–698. https://doi.org/10.1016/j.bcp.2004.05.011.

59. Vlodavsky, E., & Soustiel, J. F. (2007). Immunohistochemical expression of peripheral benzodiazepine receptors in human astrocytomas and its correlation with grade of malignancy, proliferation, apoptosis and survival. Journal of neuro-oncology, 81(1), 1–7. https://doi.org/10.1007/s11060-006-9199-9.

60. Curry, R. N., Aiba, I., Meyer, J., Lozzi, B., Ko, Y., Mcdonald, M. F., Rosenbaum, A., Cervantes, A., Huang-Hobbs, E., Cocito, C., Greenfield, J. P., Jalali, A., Gavvala, J., Mohila, C., Serin Harmanci, A., Noebels, J., Rao, G., & Deneen, B. (2023). Glioma epileptiform activity and progression are driven by IGSF3-mediated potassium dysregulation. Neuron, 111(5), 682–695.e9. https://doi.org/10.1016/j.neuron.2023.01.013.

61. Tallarico, M., Pisano, M., Leo, A., Russo, E., Citraro, R., & De Sarro, G. (2023). Antidepressant drugs for Seizures and Epilepsy: where do we Stand?. Current neuropharmacology, 21(8), 1691–1713. https://doi.org/10.2174/1570159X20666220627160048.

62. Elias, A. F., Lin, B. C., & Piggott, B. J. (2023). Ion Channels in Gliomas-From Molecular Basis to Treatment. International journal of molecular sciences, 24(3), 2530. https://doi.org/10.3390/ijms24032530.

63. Hisaoka, K., Nishida, A., Takebayashi, M., Koda, T., Yamawaki, S., & Nakata, Y. (2004). Serotonin increases glial cell line-derived neurotrophic factor release in rat C 6 glioblastoma cells. Brain research, 1002(1–2), 167–170. https://doi.org/10.1016/j.brainres.2004.01.009.

64. Li, L., Zhang, C., Wang, Z., Guo, Y., Wang, Y., Fan, X., & Jiang, T. (2022). Expression changes in ion channel and immunity genes are associated with glioma-related epilepsy in patients with diffuse gliomas. Journal of cancer research and clinical oncology, 148(10), 2793–2802. https://doi.org/10.1007/s00432-022-04049-3.

65. Sontheimer H. (2008). A role for glutamate in growth and invasion of primary brain tumors. Journal of neurochemistry, 105(2), 287–295. https://doi.org/10.1111/j.1471–4159.2008.05301.x.

66. Eckel-Passow, J. E., Lachance, D. H., Molinaro, A. M., Walsh, K. M., Decker, P. A., Sicotte, H., Pekmezci, M., Rice, T., Kosel, M. L., Smirnov, I. V., Sarkar, G., Caron, A. A., Kollmeyer, T. M., Praska, C. E., Chada, A. R., Halder, C., Hansen, H. M., Mccoy, L.S., Bracci, P. M., Marshall, R., … Jenkins, R. B. (2015). Glioma Groups Based on 1p/19q, IdH, and TERT promoter Mutations in Tumors. The New England journal of medicine, 372(26), 2499–2508. https://doi.org/10.1056/NEJMoa1407279.

67. Xu, J., Sun, M., Wang, Y., Xie, A., & Gao, J. (2020). Identification of Hub Genes of Mesio Temporal Lobe Epilepsy and prognostic Biomarkers of Brain Low-grade Gliomas Based on Bioinformatics Analysis. Cell transplantation, 29, 963689720978722. https://doi.org/10.1177/0963689720978722.

68. Aronica, E., Leenstra, S., Jansen, G. H., Van Veelen, C. W., Yankaya, B., & Troost, D. (2001). Expression of brain-derived neurotrophic factor and tyrosine kinase B receptor proteins in glioneuronal tumors from patients with intractable epilepsy: colocalization with N-methyl-d-aspartic acid receptor. Acta neuropathologica, 101(4), 383–392. https://doi.org/10.1007/s004010000296.

69. Aronica, E., Boer, K., Becker, A., Redeker, S., Spliet, W. G., Van Rijen, P. C., Wittink, F., Breit, T., Wadman, W. J., Lopes Da Silva, F. H., Troost, D., & Gorter, J. A. (2008). Gene expression profile analysis of epilepsy-associated gangliogliomas. Neuroscience, 151(1), 272–292. https://doi.org/10.1016/j.neuroscience.2007.10.036.

70. Yang, L. G., March, Z. M., Stephenson, R. A., & Narayan, P. S. (2023). Apolipoprotein E in lipid metabolism and neurodegenerative disease. Trends in endocrinology and metabolism: TEM, 34(8), 430–445. https://doi.org/10.1016/j.tem.2023.05.002.

71. Negi, D., Granak, S., Shorter, S., O’Leary, V. B., Rektor, I., & Ovsepian, S. V. (2023). Molecular Biomarkers of Neuronal Injury in Epilepsy Shared with Neurodegenerative diseases. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics, 20(3), 767–778. https://doi.org/10.1007/s13311-023-01355-7.

72. Xu, J., Sun, M., Wang, Y., Xie, A., & Gao, J. (2020). Identification of Hub Genes of Mesio Temporal Lobe Epilepsy and prognostic Biomarkers of Brain Low-grade Gliomas Based on Bioinformatics Analysis. Cell transplantation, 29, 963689720978722. https://doi.org/10.1177/0963689720978722.

73. Nicoll, J. A., Zunarelli, E., Rampling, R., Murray, L. S., Papanastassiou, V., & Stewart, J. (2003). Involvement of apolipoprotein E in glioblastoma: immunohistochemistry and clinical outcome. Neuroreport, 14(15), 1923–1926. https://doi.org/10.1097/00001756-200310270-00008.

74. Brat, D. J., Gearing, M., Goldthwaite, P. T., Wainer, B. H., & Burger, P. C. (2001). Tau-associated neuropathology in ganglion cell tumours increases with patient age but appears unrelated to APOE genotype. Neuropathology and applied neurobiology, 27(3), 197–205. https://doi.org/10.1046/j.1365–2990.2001.00311.x.

75. Kukanov K. K., Tastanbekov M. M., Olyushin V. E., Pustovoy S. V. Surgical treatment of patients with meningiomas of the foramen magnum: immediate and long-term results. Rossiiskii neirokhirurgicheskii zhurnal im. professora A. L. Polenova. 2017;9(1):36–42. eLIBRARY ID: 41260938 EDN: REBCQI (In Russ.).

76. Kukanov K. K., Tastanbekov M. M., Olyushin V. E., Pustovoi S. V., Pryanikov M. V. Meningiomas of the foramen magnum: a review of the literature and a case report. Rossiiskii neirokhirurgicheskii zhurnal im. professora A. L. Polenova. 2015;7(1):62–72. eLIBRARY ID: 41310299 EDN: AYGUHH (In Russ.).

77. Kukanov K. K., Tastanbekov M. M., Zabrodskaya Yu. M., Ushanov V. V., Kukanova O. M., Kiyashko S. S., Ivanova N. E., Olyushin V. E. Clinical features in recurrence and progression of intracranial meningiomas. The Russian Neurosurgical Journal named after prof. A. L. polenov. 2022;15(3):55–62. (In Russ.). EDN: TCGYNW https://doi.org/DOI10.56618/20712693_2023_15_3_55

78. Kiiashko S. S., Olushin V. E., Zrelov A. A., Kukanov K. K., Sklyar S. S., Maslova L. N., Ivanova N. E. Static-dynamic disorders in patients after microsurgical resection of the cerebellopontine angle tumors: long-term results. Medical News of North Caucasus. 2022;17(1):10–14. DOI — https://doi.org/10.14300/mnnc.2022.17003 (In Russ.).

79. Vasilenko A. V., Ulitin A. Yu., Ablaev N. R., Dikonenko M. V., Mansurov A. S., Shaihov M. M. Epilepsy in glioma patients: mechanisms, management, and impact of anticonvulsant therapy. Russian Journal for personalized Medicine. 2023;3(3):38–47. https://doi.org/10.18705/2782-3806-2023-3-3-38-47 (In Russ.).

80. Vasilenko A. V., Ulitin A. Yu., Lebedev I.A., Ablaev N. R., Dikonenko M. V., Mansurov A. S., Shaikhov M. M. Epilepsy in patients with glioblastoma: Mechanisms of occurrence and problems of treatment (part 1). Medical alphabet. 2023;(14):45–50. https://doi.org/10.33667/2078-5631-2023-14-45-50 (In Russ.).

81. Vasilenko A. V., Chudievich S. N., Ulitin A. Yu., Makhortova S.A., Rasulov Z. M., Bubnova P. D., Sokolov I.A., Bulaeva M.A., Lavrovskiy P. V., Vershinin A. E., Likhachev M.A. Epilepsy associated with pituitary neuroendocrine tumors: Current status of problem and interdisciplinary approach. Medical alphabet. 2022;(21):43–50. https://doi.org/10.33667/2078-5631-2022-21-43-50 (In Russ.).

82. A. Yu. Ulitin, M. V. Macko, D. E. Macko [i dr.]. Molecular and genetic examination of patients with multiple cerebral gliomas. Translyacionnaya medicina.— 2015.— № S 2. — S. 111. — EDN YSVNZX (In Russ.).

83. Metastatic glioblastoma in submandibular lymph node (a rare case). A. Yu. Ulitin, Yu. M. Zabrodskaya, V. E. Olyushin [i dr.]. Voprosy onkologii.— 2009. — T. 55, № 2. — S. 230–236. — EDN JWWNHB (In Russ.).

84. Glioma of chiasma and optical nerves, atypical clinical case. A. Yu. Ulitin, d. M. Rostovcev, S. P. Bazhanov, A. V. Kuz'min. Palliativnaya medicina i reabilitaciya.— 2010.— № 3. — S. 51–56. — EDN MUTODV (In Russ.).