Association of IDH1 Mutation and MGMT Promotor Methylation with Clinicopathological Parameters in Adults with Gliomas in England

Background - Molecular profiles can predict which patients will respond to current standard treatment and new targeted therapy regimens. Using data from a highly diverse population of approximately three million in Southeast London and Kent, this study aims to evaluate the prevalence of IDH1 mutation and MGMT promotor methylation in the gliomas diagnosed in adult patients and to explore correlations with patients’ clinicopathological characteristics. Methods - Anonymised data on 749 adult patients diagnosed with a glioma in 2015-2019 at King’s College Hospital were extracted. Univariable and multivariable logistic regressions were used to estimate odds ratios (ORs) for expressing IDH1 mutation and MGMT promotor methylation, based on each patient’s age, sex, ethnicity, histology, tumour location and extent of excision. The Kaplan-Meier method was used to estimate the overall survival functions. Results - 19.5% of cases were IDH1 mutated. Being 39 years and younger (OR 5.48, 95% CI 3.17-9.47), from Asian/Asian British background (OR 3.68, 95% CI 1.05-12.97), having MGMT methylation (OR 15.92, 95% CI 7.30-34.75), an oligodendroglioma diagnosis (OR 7.45, 95% CI 2.90-19.13) and receiving a gross total/total microscopic excision (OR 1.95, 95% CI 1.24-3.08) were each univariately correlated with IDH1 mutation. MGMT methylation association persisted on adjustment (OR 14.13, 95% CI 3.88-51.43). MGMT promotor methylation was seen in 54.3 % of gliomas. In the univariate adjusted ORs, being younger than 39 years (OR 2.56, 95% CI 1.48-4.43), female (OR 1.52, 95% CI 1.11-2.08), having IDH1 mutation (OR 15.92, 95% CI 7.30-34.75) and an oligodendroglioma diagnosis (OR 6.20, 95% CI 1.33-28.88) were associated with MGMT methylation. Being female (OR 1.75, 95% CI 1.22-2.51) and having an IDH1 mutation (OR 15.54, 95% CI 4.73-51.05) persisted after adjustment for age, sex, ethnicity, histology, tumour location and extent of excision. IDH1 mutant and MGMT methylated gliomas were associated with frontal lobe location. Survival analysis showed that patients with both IDH1 mutation and MGMT methylation had a significantly better survival than those with either molecular marker alone. Over a 3-year period, women with unmethylated MGMT promotor generally had a better survival than men with unmethylated MGMT. Conclusion - This study showed that the molecular markers IDH1 mutation and MGMT promotor methylation were associated with age, sex, Asian/Asian British Ethnic Group, tumour histology, anatomical location and extent of excision. This study has demonstrated the importance of assessing glioma molecular markers in the clinical setting, and the need to stratify patients according to their clinicopathological characteristics.