Article detail · 2018
Use of telomerase promoter mutations to mark specific molecular subsets with reciprocal clinical behavior in IDH mutant and IDH wild-type diffuse gliomas
- Year
- 2018
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue JOURNAL OF NEUROSURGERY
- Catalog match (ISSN) Journal of Neurosurgery
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
OBJECTIVE Recent studies have established that hemispheric diffuse gliomas may be grouped into subsets on the basis of molecular markers; these subsets are loosely correlated with the histopathological diagnosis but are strong predictors of clinical tumor behavior. Based on an analysis of molecular and clinical parameters, the authors hypothesized that mutations of the telomerase promoter (TERTp-mut) mark separate oncogenic programs among isocitrate dehydrogenase 1 and/or 2 (IDH) mutant (IDH-mut) and IDH wild-type (IDH-wt) diffuse gliomas independent of histopathology or WHO grade. METHODS Four molecular subsets of the combined statuses of IDH and TERT-promoter mutations (double mutant, IDH only, TERT only, and double negative) were defined. Differences in age, anatomical location, molecular genetics, and survival rates in a surgical cohort of 299 patients with a total of 356 hemispheric diffuse gliomas (WHO Grade II, III, or IV) were analyzed. RESULTS TERTp-mut were present in 38.8% of IDH-mut and 70.2% of IDH-wt gliomas. The mutational status was stable in each patient at 57 recurrence events over a 2645-month cumulative follow-up period. Among patients with IDH-mut gliomas, those in the double-mutant subset had better survival and a lower incidence of malignant degeneration than those in the IDH-only subset. Of patients in the double-mutant subset, 96.3% were also positive for 1p/19q codeletions. All patients with 1p/19q codeletions had TERTp-mut. In patients with IDH-mut glioma, epidermal growth factor receptor or phosphatase and tensin homolog mutations were not observed, and copy-number variations were uncommon. Among IDH-wt gliomas, the TERT-only subset was associated with significantly higher age, higher Ki-67 labeling index, primary glioblastoma-specific oncogenic changes, and poor survival. The double-negative subset was genetically and biologically heterogeneous. Survival analyses (Kaplan-Meier, multivariate, and regression-tree analyses) confirmed that patients in the 4 molecular subsets had distinct prognoses. CONCLUSIONS Molecular subsets result in different tumor biology and clinical behaviors in hemispheric diffuse gliomas.
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Citations
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37 citations
OpenAlex cited_by_count (cache / database)
18 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
- Identification of IDH and TERTp mutation status using 1 H-MRS in 112 hemispheric diffuse gliomas. 2020
- Identification of IDH and TERTp mutation status using 1H‐MRS in 112 hemispheric diffuse gliomas 2019
- Whole exome sequencing–based analysis to identify DNA damage repair deficiency as a major contributor to gliomagenesis in adult diffuse gliomas 2020
- Whole exome sequencing-based analysis to identify DNA damage repair deficiency as a major contributor to gliomagenesis in adult diffuse gliomas. 2019
- Whole exome sequencing–based analysis to identify DNA damage repair deficiency as a major contributor to gliomagenesis in adult diffuse gliomas 2019
- Whole exome sequencing-based analysis to identify DNA damage repair deficiency as a major contributor to gliomagenesis in adult diffuse gliomas. 2019
- Identification of IDH and TERTp mutations using dynamic susceptibility contrast MRI with deep learning in 162 gliomas 2024
- Correlation of anatomical involvement patterns of insular gliomas with subnetworks of the limbic system. 2022
- Magnetic resonance spectroscopic correlates of progression free and overall survival in “glioblastoma, IDH-wildtype, WHO grade-4” 2023
- Mutations and Copy Number Alterations in IDH Wild-Type Glioblastomas Are Shaped by Different Oncogenic Mechanisms 2020