Combined analysis of
 TERT
 ,
 EGFR
 , and
 IDH
 status defines distinct prognostic glioblastoma classes

Labussière, Marianne; Boisselier, Blandine; Mokhtari, Karima; Stefano, Anna Luisa Di; Rahimian, Anais; Rossetto, Marta; Ciccarino, Pietro; Saulnier, Olivier; Paterra, Rosina; Marie, Yannick; Finocchiaro, Gaetano; Sanson, Marc

doi:10.1212/wnl.0000000000000814

Cited by 196 publications

(159 citation statements)

References 27 publications

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“…In the present study, TERT promoter mutations were identified in 64% of GBMs, and were associated with the age and sex of patients with GBM. These results are consistent with those of previous studies (4,5). The association between TERT promoter mutations and other genetic alterations has been observed in previous studies (4,5).…”

Section: Discussionsupporting

confidence: 93%

“…Previous studies demonstrated that the association between telomere length and TERT expression is complex and may be regulated by a number of other factors, including the activities of signaling pathways and alterations of genes (4,28,29). Previous studies have demonstrated that TERT promoter is the most common type of mutation in GBMs, suggesting that it may be an early event in GBM carcinogenesis (2,4,5,(30)(31)(32). In the present study, TERT promoter mutations were identified in 64% of GBMs, and were associated with the age and sex of patients with GBM.…”

Section: Discussionmentioning

confidence: 99%

“…In spite of radical surgery combined with concomitant chemoradiation therapy based on temozolomide, the median survival rate of patients with GBM remains ~1 year (2). Furthermore, clinical trials have demonstrated only limited benefits of targeted regimens, indicating that the identification of the genetic and molecular characteristics of GBM is required to develop more effective treatment strategies (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

“…Genetic studies including a large number of patients with GBM have revealed various genetic alterations in GBM, including isocitrate dehydrogenase gene mutations and mutations in the promoter region of telomerase reverse transcriptase gene (TERT) (4,5). Of these, TERT promoter mutations have been identified in a subpopulation of GBM and were revealed to be significantly associated with poor clinical prognosis (2,5,6).…”

Section: Introductionmentioning

confidence: 99%

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Preclinical and clinical implications of TERT promoter mutation in glioblastoma multiforme

et al. 2017

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Abstract. The promoter region of the telomerase reverse transcriptase gene (TERT) is mutated in a subpopulation of patients with glioblastoma multiforme (GBM). In the present study, preclinical and clinical implications of the mutation were analyzed in 25 GBMs to evaluate its utility as a therapeutic target. Associations between the TERT promoter mutation and a number of preclinical/clinical characteristics were analyzed. Notably, the TERT promoter mutation was identified in 92.3% of GBMs where dissociated cells revealed in vitro sphere formation capacity; while the TERT promoter mutation was identified in 33.3% of GBMs without in vitro sphere formation capacity (P= 0.004). In addition, this significantly increased mutation rate was observed in GBMs with in vivo tumorigenic potential (80% vs. 0%; P= 0.004). Furthermore, patients with GBM exhibiting the TERT promoter mutation demonstrated significantly decreased overall survival rate compared with patients lacking this mutation (81.7 vs. 152.6 weeks; P=0.026). The results of the present study indicated that the TERT promoter mutation is associated with the self-renewal capacity of GBM cells and clinical aggressiveness of GBMs, which may be translated to a targeting therapy against TERT to inhibit the self-renewal of GBM cells.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preclinical and clinical implications of TERT promoter mutation in glioblastoma multiforme

et al. 2017

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“…We did not find that the TERT promoter mutation status is an independent prognostic biomarker of primary GBM, even though the TERT mutation status analyses revealed borderline significance in the univariate survival analysis (Figure 3E). However, some GBM studies that included both primary and secondary GBM patients suggested that TERT promoter mutations are independently associated with a negative prognosis 19, 20. We speculate that the prognostic value of TERT promoter mutations in relation to poor survival is partly due to the IDH status.…”

Section: Discussionmentioning

confidence: 81%

The TERT promoter mutation status and MGMT promoter methylation status, combined with dichotomized MRI‐derived and clinical features, predict adult primary glioblastoma survival

et al. 2018

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PurposeThis study aimed to integrate the TERT promoter mutation status, MGMT promoter methylation status, MRI‐derived features, and clinical features into a survival analysis model to better understand adult primary glioblastoma prognosis‐related markers.MethodA total of 304 adult glioblastoma samples collected after surgical resection were selected for retrospective analysis, and Sanger sequencing was performed to detect IDH and TERT promoter mutations. The methylation of the MGMT promoter was analyzed by pyrosequencing, and MRI‐derived and clinical features were dichotomized into easily acquired variables. Random survival forest analysis, Kaplan‐Meier analysis, Cox proportional hazard regression, and LASSO regression were performed for the survival analysis, and ROC analysis and Pearson's chi‐squared test were employed for the correlation analysis.ResultsWild‐type IDH was present in 89.8% of the adult glioblastoma samples, and TERT promoter mutations and MGMT promoter methylation were observed in 66.42% and 38.49% of all adult primary glioblastomas, respectively. Age and MGMT promoter methylation were identified as independent prognostic biomarkers, and the TERT promoter mutation status and MGMT promoter methylation status, when combined with other tumor‐related factors, generated several different survival subgroups. None of the factors investigated in this study predicted the MGMT promoter status, and MRI‐detected necrosis was positively associated with TERT promoter mutations.ConclusionMGMT promoter methylation and TERT promoter mutations, combined with MRI‐derived and clinical features, revealed different survival subgroups with distinct responses to current treatments, and this information increases the ability to predict the survival of adult primary glioblastoma patients. MRI‐detected necrosis often indicates the presence of TERT promoter mutations.

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Intraoperative rapid molecular diagnosis aids glioma subtyping and guides precise surgical resection

Li,

Han,

et al. 2024

Ann Clin Transl Neurol

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ObjectiveThe molecular era of glioma diagnosis and treatment has arrived, and a single rapid histopathology is no longer sufficient for surgery. This study sought to present an automatic integrated gene detection system (AIGS), which enables rapid intraoperative detection of IDH/TERTp mutations.MethodsA total of 78 patients with gliomas were included in this study. IDH/TERTp mutations were detected intraoperatively using AIGS in 41 of these patients, and they were guided to surgical resection (AIGS detection group). The remaining 37 underwent histopathology‐guided conventional surgical resection (non‐AIGS detection group). The clinical utility of this technique was evaluated by comparing the accuracy of glioma subtype diagnosis before and after TERTp mutation results were obtained by pathologists and the extent of resection (EOR) and patient prognosis for molecular pathology‐guided glioma surgery.ResultsWith NGS/Sanger sequencing and chromosome detection as the gold standard, the accuracy of AIGS results was 100%. And the timing was well matched to the intraoperative rapid pathology report. After obtaining the TERTp mutation detection results, the accuracy of the glioma subtype diagnosis made by the pathologists increased by 19.51%. Molecular pathology‐guided surgical resection of gliomas significantly increased EOR (99.06% vs. 93.73%, p < 0.0001) and also improved median OS (26.77 vs. 13.47 months, p = 0.0289) and median PFS (15.90 vs. 10.57 months, p = 0.0181) in patients with glioblastoma.InterpretationUsing AIGS intraoperatively to detect IDH/TERTp mutations to accurately diagnose glioma subtypes can help achieve maximum safe resection of gliomas, which in turn improves the survival prognosis of patients.

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Combined analysis of TERT , EGFR , and IDH status defines distinct prognostic glioblastoma classes

Abstract: The analysis of TERTp-mut, in combination with EGFR amplification and IDH mutation status, refines the prognostic classification of GBMs.

Cited by 196 publications

References 27 publications

Preclinical and clinical implications of TERT promoter mutation in glioblastoma multiforme

Preclinical and clinical implications of TERT promoter mutation in glioblastoma multiforme

The TERT promoter mutation status and MGMT promoter methylation status, combined with dichotomized MRI‐derived and clinical features, predict adult primary glioblastoma survival

Intraoperative rapid molecular diagnosis aids glioma subtyping and guides precise surgical resection

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