IDH mutations but not TERTp mutations are associated with seizures in lower-grade gliomas

Abstract

Glioma is the most common malignant tumor in the central nervous system (CNS). Lower-grade gliomas (LGG) refer to Grade II and III gliomas. In LGG patients, seizure often appears as an initial symptom and play an important role in clinical performance and quality of life of the patients. To date, the relationship between the onset of seizures and the molecular pathology in gliomas is still poorly investigated. In this study, we investigate the potential relationship between isocitrate dehydrogenase (IDH)/telomerase reverse transcriptase promoter (TERTp) mutations and preoperative seizures in patients with LGG. 289 adult LGG patients were enrolled in this study. Data of clinical characteristics and molecular pathology were acquired. Sanger sequencing was used to detect IDH/TERTp mutations. Chi-square test was performed to determine if the IDH/TERTp mutations were associated with seizures and seizure types. In 289 LGG patients, preoperative seizures accounted for 25.3% (73/289), IDH mutations accounted for 34.3%(99/289), and TERTp mutations accounted for 44.3% (128/289). The correlation analysis demonstrated that IDH mutation is a significant factor influencing the occurrence of tumor-related epilepsy (P <.001, chi-square test). On the other hand, the statistical analysis revealed no significant correlation between TERTp mutations and seizure in LGG patients (P = .102, chi-square test). The tumor-related epilepsy rates vary among different subgroups according to IDH/TERTp mutations. However, there is no definite correlation between the IDH (P = 1.000, chi-square test)/TERTp (P = .613, chi-square test) mutations and the types of epileptic seizure. IDH mutations are more common in preoperative LGG patients with epileptic symptoms, suggesting that this mutation is positively correlated with seizures. However, there was no significant correlation between TERTp mutations and seizures. Different molecular pathologic types based on IDH/TERTp have different incidences of tumor-associated epilepsy in LGGs.

Figure 1

Correlation analysis between molecular pathology typing of IDH/TERTp and the incidence of tumor-related epilepsy. (A) Correlation analysis demonstrates epilepsy rate was significant higher in IDH mutation group than IDH wildtype group (P <.001, chi-square test).(B) Correlation analysis demonstrates that the epilepsy rate in the TERTp mutation group was not significantly correlated with the TERTp wildtype group (P = .102, chi-square test).(C) Correlation analysis demonstrates that the epilepsy rate in the IDH mut/TERTp mut group was not significantly correlated with the IDH wt/TERTp wt group (P = .092, chi-square test), (D) in the IDH mut/TERTp mut group was not significantly correlated with the IDH mut /TERTp wt group (P = .221, chi-square test).(E) Correlation analysis demonstrates epilepsy rate was significant higher in IDH mut/TERTp mut group than IDH wt/TERTp mut group (P = .010, chi-square test),(F) and in IDH mut /TERTp wt group than IDH wt/TERTp wt group (P <.001, chi-square test),(G) in the IDH wt/TERTp wt group was not significantly correlated with the IDH wt /TERTp mut group (P = .246, chi-square test). (H) Correlation analysis demonstrates epilepsy rate was significant higher in IDH mut/TERTp wt group than IDH wt/TERTp mut group (P <.001, chi-square test). IDH = isocitrate dehydrogenase, TERTp = telomerase reverse transcriptase promoter.

Figure 2

Correlation analysis between molecular pathological typing of IDH/TERTp and types of seizures. (A) Correlation analysis demonstrates that the seizure types was not significantly correlated with IDH mutations (P = 1.000, chi-square test). (B) Correlation analysis demonstrates that the seizure types was not significantly correlated with TERT mutations (P = .613, chi-square test). (C) T-test results showed that there was no significant correlation between tumor volume and seizures (P = .504, t test). IDH = isocitrate dehydrogenase, TERTp = telomerase reverse transcriptase promoter.