The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis

Vuong, Huy Gia; Nguyen, Thu Quynh; Ngo, Tam N.M.; Nguyen, Hoang Cong; Fung, Kar‐Ming; Dunn, Ian F.

doi:10.1186/s12885-020-07364-5

Cited by 31 publications

(8 citation statements)

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“… 12 That the effect of the TERT promoter mutation on patient survival can be modulated by IDH mutation and other genetic events in glioma patients has been suggested in prior studies. 34 , 35 , 36 …”

Section: Discussionmentioning

confidence: 99%

Prognostic importance of IDH mutations in chondrosarcoma: An individual patient data meta‐analysis

2021

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Introduction IDH1/2 mutations are prevalent in cartilaginous tumors including chondrosarcoma. This meta‐analysis using individual patient data (IPD) aimed to investigate the clinical and prognostic association of these mutations in chondrosarcoma patients. Methods Two electronic databases including PubMed and Web of Science were searched for relevant data. We included studies providing IPD of chondrosarcoma with available IDH1/2 mutational status for meta‐analysis. Chi‐square and t‐test were performed to compare the groups with and without IDH1/2 mutations. For survival analysis, log‐rank test, and Cox proportional hazards model were used to investigate the association of IDH mutations with patient outcomes. Results Fourteen studies with 488 patients were analyzed. IDH1 and IDH2 mutations were detected in 38.7% and 12.1% of cases, respectively. IDH1/2 mutations were significantly associated with an older age (p = 0.003), tumor origins (p < 0.001), tumor grades (p < 0.001), larger diameter (p = 0.003), relapse (p = 0.014), and patient mortality (p = 0.04). Multivariate Cox regression analysis adjusted for age, gender, tumor grade, and tumor sites confirmed the negative impact of IDH1/2 mutations on patient overall survival (HR = 1.90; 95% CI = 1.06–3.42; p = 0.03). Conclusion Our meta‐analysis demonstrated the distinct characteristics of IDH1/2‐mutated chondrosarcomas in comparison to those without mutations. These mutations could serve as an independent prognostic biomarker to better prognosticate patient outcomes and design appropriate treatment plans.

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Section: Discussionmentioning

confidence: 99%

Prognostic importance of IDH mutations in chondrosarcoma: An individual patient data meta‐analysis

2021

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“…Of interest, several studies found a prognostic interaction of TERT promoter mutation with MGMT promoter methylation in patients with IDHwt glioblastoma treated with radiochemotherapy [ 16 , 17 ]. Furthermore, a recent meta-analysis with low-grade glioma as well as glioblastoma patients including the aforementioned studies showed that among TERT promotor mutated low-grade gliomas, MGMT promotor methylation was associated with improved overall survival [ 18 ]. However, no IDH-status was evaluated in this retrospective subgroup analysis.…”

Section: Discussionmentioning

confidence: 99%

Extent, pattern, and prognostic value of MGMT promotor methylation: does it differ between glioblastoma and IDH-wildtype/TERT-mutated astrocytoma?

et al. 2021

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Introduction The cIMPACT-NOW update 6 first introduced glioblastoma diagnosis based on the combination of IDH-wildtype (IDHwt) status and TERT promotor mutation (pTERTmut). In glioblastoma as defined by histopathology according to the WHO 2016 classification, MGMT promotor status is associated with outcome. Whether this is also true in glioblastoma defined by molecular markers is yet unclear. Methods We searched the institutional database for patients with: (1) glioblastoma defined by histopathology; and (2) IDHwt astrocytoma with pTERTmut. MGMT promotor methylation was analysed using methylation-specific PCR and Sanger sequencing of CpG sites within the MGMT promotor region. Results We identified 224 patients with glioblastoma diagnosed based on histopathology, and 54 patients with IDHwt astrocytoma with pTERTmut (19 astrocytomas WHO grade II and 38 astrocytomas WHO grade III). There was no difference in the number of MGMT methylated tumors between the two cohorts as determined per PCR, and also neither the number nor the pattern of methylated CpG sites differed as determined per Sanger sequencing. Progression-free (PFS) and overall survival (OS) was similar between the two cohorts when treated with radio- or chemotherapy. In both cohorts, higher numbers of methylated CpG sites were associated with favourable outcome. Conclusions Extent and pattern of methylated CpG sites are similar in glioblastoma and IDHwt astrocytoma with pTERTmut. In both tumor entities, higher numbers of methylated CpG sites appear associated with more favourable outcome. Evaluation in larger prospective cohorts is warranted.

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“…Secondly, the sample size of the study included in this study was small, especially G3 gliomas, and grade and grade gliomas were not included. In addition, we did not have data for O6-methylguanine-DNA methyltransferase (MGMT) methylation status and telomerase reverse transcriptase (TERT) promoter status, both of which play an important role in patients with gliomas 27 . Therefore, multi-center prospective studies, further molecular pathology experimental analyses, large sample researches of HGGs are required.…”

Section: Limitationsmentioning

confidence: 99%

The Diagnostic Value of Preoperative Hematology Makers in the Classification and Molecular Subtypes of Newly Diagnosed High-Grade Gliomas

Xing

Zhai

Yang

et al. 2021

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Purpose: The purpose of our study is to explore the diagnostic value of the single and combined hematological maker for the classification and isocitrate dehydrogenase (IDH)-1/2 mutations (IDH) molecular subtypes of high-grade gliomas (HGGs).Methods: A total of 354 newly diagnosed HGGs patients were included in this study. Firstly, we compared the levels of hematology indicators in the classification and molecular subtypes of HGGs. Next, the correlation between the levels of hematology indicators with basic clinical features was analyzed. Finally, the diagnostic value of the single and combined hematology indicator for identifying the classification and molecular subtypes from HGGs was performed.Results: The level of fibrinogen (FIB) was higher in higher grade gliomas and glioblastoma multiforme IDH wild type (GBM IDH-wt). Nutrition-related indicators such as serum albumin (ALB), albumin/globulin ratio (AGR), and prognostic nutrition index (PNI) were negatively correlated with age, whereas FIB was positively associated with age. Compared with women, men with GBM had significantly higher AGR and lower serum globulin (GLOB). We found that the best single and combined indicator for identifying GBM and GBM IDH-wt from HGGs were FIB [0.595 (0.519-0.672) and 0.615 (0.546-0.684)] and age+FIB [0.712 (0.642-0.783) and 0.726 (0.662-0.791)], respectively.Conclusions: Preoperative hematological indicators have high diagnostic value for GBM and GBM IDH-wt from HGGs, especially FIB combined age.

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The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis

Cited by 31 publications

References 59 publications

Prognostic importance of IDH mutations in chondrosarcoma: An individual patient data meta‐analysis

Prognostic importance of IDH mutations in chondrosarcoma: An individual patient data meta‐analysis

Extent, pattern, and prognostic value of MGMT promotor methylation: does it differ between glioblastoma and IDH-wildtype/TERT-mutated astrocytoma?

The Diagnostic Value of Preoperative Hematology Makers in the Classification and Molecular Subtypes of Newly Diagnosed High-Grade Gliomas

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