Сибирский онкологический журнал (Sep 2020)

GENETIC BIOMARKERS OF GLIAL BRAIN TUMORS: IDH1 AND IDH2 MUTATIONS

  • M. Yu. Prokudin,
  • B. V. Martynov,
  • D. V. Svistov,
  • I. V. Litvinenko,
  • E. N. Imyanitov,
  • V. S. Chirsky,
  • S. E. Bushurov,
  • A. I. Yakovenko,
  • K. A. Chemodakova,
  • O. A. Klitsenko,
  • O. A. Gorustovich,
  • G. F. Medvedeva,
  • A. R. Bulatov

DOI
https://doi.org/10.21294/1814-4861-2020-19-4-59-66
Journal volume & issue
Vol. 19, no. 4
pp. 59 – 66

Abstract

Read online

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.

Keywords