GENETIC BIOMARKERS OF GLIAL BRAIN TUMORS: IDH1 AND IDH2 MUTATIONS

• Published in: Sibirskiĭ onkologicheskiĭ zhurnal Vol. 19; no. 4; pp. 59 - 66
• Main Authors: Prokudin, M. Yu, Martynov, B. V., Svistov, D. V., Litvinenko, I. V., Imyanitov, E. N., Chirsky, V. S., Bushurov, S. E., Yakovenko, A. I., Chemodakova, K. A., Klitsenko, O. A., Gorustovich, O. A., Medvedeva, G. F., Bulatov, A. R.
• Format: Journal Article
• Language: English
• Published: Russian Academy of Sciences, Tomsk National Research Medical Center 02.09.2020
• Subjects: anaplastic astrocytoma; brain tumors; diffuse astrocytoma; epilepsy; glioblastoma; gliomas; idh1 and idh2 gene mutations; seizure
• ISSN: 1814-4861; 2312-3168
• DOI: 10.21294/1814-4861-2020-19-4-59-66

Introduction. Mutations in the isocytrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are considered driver genetic events in gliomas. Their frequency reaches 7080 % in low-grade gliomas and in secondary glioblastomas, and their oncogenic effect is realized by accumulation of the metabolite 2-hydroxyglutarate, which disrupts DNA and protein methylation processes. The aim of the study was to analyze the associations between the presence of IDH1/2 mutations and clinical and morphological parameters of glial tumors. Material and Methods. The study included 147 patients with glial brain tumors. Associations between IDH1/2 status and tumor histological type, age of disease onset, tumor localization, and clinical manifestations were investigated. Results. Gliomas containing IDH1/2 mutations were characterized by a younger age at diagnosis (mean: 39.5 years) compared to IDH-negative cases (47.2 years) (p<0.01). IDH1/2-mutated tumors were more often localized in the frontal (53.4 %) and parietal lobes (61.3 %) than in the other areas of the brain (p<0.05). It was demonstrated that the incidence of epilepsy was significantly higher among patients with IDH1/2 genetic defects (69.2 % vs. 48.2 %, p<0.05). Patients with IDH1/2 mutations had more favorable course of the disease. Among individuals with a combination of these factors (localization of the tumor in the frontal or parietal lobe, presence of epilepsy, age younger than 39 years), the frequency of IDH1/2 mutations reached 21/27 (77.8 %), which was significantly higher than that in all other patients (44/119 (37.0 %), OR = 5.97, 95 % CI: 2.2415.91, p<0.001). Conclusion. The presence of IDH1/2 genetic defects is associated with localization of glial tumors in the frontal and parietal lobes of the brain, earlier age at disease onset and the presence of epileptic syndrome.