IDH1/2 Mutations in Patients With Diffuse Gliomas: A Single Centre Retrospective Massively Parallel Sequencing Analysis

Abstract

Patients below 55 years were genetically studied because the prevalence of isocitrate dehydrogenase 1 (IDH1) decreases in older patients and on grounds of cost-effectiveness, as suggested by the World Health Organization (WHO) in 2016. The aim of our study was to use novel massively parallel sequencing (MPS) approaches to examine rare variants of IDH1/2 in Czech diffuse astrocytic and oligodendroglial tumors (gliomas) patients below 55 years of age who had been immunohistochemically (IHC) diagnosed as IDH1 R132H negative. The IHC IDH1 status (wild type or mutant) of 275 tissue samples was analyzed using antibodies against the IDH1 R132H protein. Sixty-three samples of 55 years old patients with IHC IDH1 WT status were genotyped using two different MPS technologies to detect rare IDH1 and IDH2 variants. The tiered IHC (60 positive) and molecular (10 positive) approach thus revealed that 70 of the 275 samples (25%) bore IDH1/IDH2 mutations. The combined molecular and IHC approach thus revealed that 70 of the 275 samples (25%) considered in the study bore IDH1/IDH2 mutations. IHC detection of the IDH1 R132H variant should be routinely complemented with MPS to detect rare IDH1/2 variants in glioma patients below 55 years of age with negative IHC result of IDH R132H variant.

TTC7B Is a Novel Prognostic-Related Biomarker in Glioma Correlating with Immune Infiltrates and Response to Oxidative Stress by Temozolomide

“…This research also compared the similarities between IDH1 and TTC7B expressions. As indicated by WHO, IDH1 phenotypes serve as a unique diagnostic technique for clinical usage and categorization of diffuse gliomas among adults is mostly determined by IDH1 mutation status [ 3 , 24 , 25 ]. In this study, we investigated the differences between IDH1 wild type and IDH1 -R132 mutant groups.…”

Association of IDH1 Mutations with Epilepsies in Patients with Diffuse Adult Glioma according to the WHO 2021 Classification

“…In diffuse astrocytomas, the percentage of IDH1 mutations was 76.7%, while in glioblastoma, this percentage was 5.6% [14]. Furthermore, a more recent study that included astrocytic and oligodendroglial tumors proved the presence of IDH1 mutations in 60% of diffuse astrocytomas, 33% of anaplastic astrocytomas, 67% of anaplastic oligodendrogliomas, and 5% of glioblastomas [15]. An earlier meta-analysis analyzing IDH1 and IDH2 mutations from 55 different studies with 9487 glial tumors showed that both mutations were independently and statistically significantly associated with better overall survival and progression of free survival and disease-free survival in glioma patients [16].…”

Effects of Reoperation Timing on Survival among Recurrent Glioblastoma Patients: A Retrospective Multicentric Descriptive Study

“…Isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were assessed using standard techniques employed at the three neuro-oncology centers described in detail in previous reports [19][20][21]. Briefly, immunohistochemistry (anti-IDH1R132H) and genotyping with Next-Generation Sequencing (Nextera XT kit, Illumina, San Diego, CA, USA) were employed for IDH mutation analyses and real-time methylation-specific PCRs or pyrosequencing analysis of MGMT promoter methylation.…”