Incidence of biomarkers in high-grade gliomas and their impact on survival in a diverse SouthEast Asian cohort - a population-based study

Samantha Ya Lyn Ang,Nicolas Kon Kam King,Angela An Qi See,Beng Ti Ang,Lester Lee,Ting Yao Ang

doi:10.1186/s12885-020-6536-x

Abstract

BackgroundGliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population.MethodsRecords of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients’ age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test.Results181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006).ConclusionsThe incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.

Highlights

Gliomas consist of a heterogeneous group of tumors
This study aimed to report the incidences of four molecular biomarkers in high-grade gliomas in an ethnically diverse Southeast Asian population, which have far not been reported
Grade IV glioma patients with IDH1 mutation had a median overall survival of 46.9 months compared to 50.2 months for those who tested negative (p = 0.22)

Summary

Introduction

Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. Gliomas are the most prevalent primary brain malignancy, accounting for more than 80% of primary brain tumors [1] They are a highly heterogeneous group of tumors arising from glial cells in the central nervous system [2]. Molecular signatures of gliomas have shown that histologically distinct tumor subtypes might share common precursor cells, while histologically indistinguishable gliomas could be separated into biologically and molecularly distinct classes [9]. These molecular markers might serve as prognostic and predictive markers, indicators of disease aggressiveness and treatment response, and potential therapeutic targets [10, 11]. Examples include hypermethylation of O6-methylguanine-DNA-methyltransferase (MGMT), 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations 1 and 2, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX)

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