TERT promoter mutation and its interaction with IDH mutations in glioma: Combined TERT promoter and IDH mutations stratifies lower-grade glioma into distinct survival subgroups—A meta-analysis of aggregate data

2017 ◽  
Vol 120 ◽  
pp. 1-9 ◽  
Author(s):  
Huy Gia Vuong ◽  
Ahmed M.A. Altibi ◽  
Uyen N.P. Duong ◽  
Hanh T.T. Ngo ◽  
Thong Quang Pham ◽  
...  
2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi16-vi16
Author(s):  
Yoshinobu Takahashi ◽  
Hayato Takeuchi ◽  
Seisuke Tanigawa ◽  
Takanari Okamoto ◽  
Naoya Hashimoto

Abstract Background and Purpose: In the cIMPACT-Now update 3, it was proposed that grade 2 astrocytic gliomas without IDH-mutations and grade 3 astrocytic gliomas with TERT promoter mutations should be designated as diffuse IDH wildtype astrocytic glioma with molecular features of WHO grade IV glioblastoma. Therefore, we investigated whether this group of tumors actually corresponds to grade IV prognostically in cases that we encountered ourselves. Cases and Methods: Among the 65 patients having primary astrocytic glioma who were operated in our hospital from January 2016 to March 2021, the prognostic values of seven patients with lower-grade glioma, IDH wildtype, and pTERT mutant were investigated. Results: Among the seven patients, the median age was 59 years (50–66 years). Four of them had anaplastic astrocytoma, two had diffuse astrocytoma, and no tumor lesion could be identified upon histological examination for one patient. The male-to-female ratio was 1:6. MGMT methylation was observed in two patients (29%). The median survival was 20 months, with a significantly worse prognosis when compared with lower-grade glioma without the TERT promoter mutation (13 patients: median survival 40 months), but a better prognosis when compared with glioblastoma (45 patients: median survival 13 months) (Log-rank p = 0.0051). Conclusion: Although EGFR amplification, combined whole chromosome 7 gain, and whole chromosome 10 loss were not examined, the prognostic value of lower-grade glioma, IDH wildtype, and pTERT mutant was not as poor as that of glioblastoma. Further investigation is required to confirm whether these groups of tumors should be treated in the same way as grade IV glioblastoma.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zhenxing Huang ◽  
Changyu Lu ◽  
Gen Li ◽  
Zhenye Li ◽  
Shengjun Sun ◽  
...  

ObjectivesTo explore whether a simplified lesion delineation method and a set of diffusion tensor imaging (DTI) metric-based histogram parameters (mean, 25th percentile, 75th percentile, skewness, and kurtosis) are efficient at predicting the molecular pathology status (MGMT methylation, IDH mutation, TERT promoter mutation, and 1p19q codeletion) of lower grade insular gliomas (grades II and III).Methods40 lower grade insular glioma patients in two medical centers underwent preoperative DTI scanning. For each patient, the entire abnormal area in their b-non (b0) image was defined as region of interest (ROI), and a set of histogram parameters were calculated for two DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD). Then, we compared how these DTI metrics varied according to molecular pathology and glioma grade, with their predictive performance individually and jointly assessed using receiver operating characteristic curves. The reliability of the combined prediction was evaluated by the calibration curve and Hosmer and Lemeshow test.ResultsThe mean, 25th percentile, and 75th percentile of FA were associated with glioma grade, while the mean, 25th percentile, 75th percentile, and skewness of both FA and MD predicted IDH mutation. The mean, 25th percentile, and 75th percentile of FA, and all MD histogram parameters significantly distinguished TERT promoter status. Similarly, all MD histogram parameters were associated with 1p19q status. However, none of the parameters analyzed for either metric successfully predicted MGMT methylation. The 25th percentile of FA yielded the highest prediction efficiency for glioma grade, IDH mutation, and TERT promoter mutation, while the 75th percentile of MD gave the best prediction of 1p19q codeletion. The combined prediction could enhance the discrimination of grading, IDH and TERT mutation, and also with a good fitness.ConclusionsOverall, more invasive gliomas showed higher FA and lower MD values. The simplified ROI delineation method presented here based on the combination of appropriate histogram parameters yielded a more practical and efficient approach to predicting molecular pathology in lower grade insular gliomas. This approach could help clinicians to determine the extent of tumor resection required and reduce complications, enabling more precise treatment of insular gliomas in combination with radiotherapy and chemotherapy.


2020 ◽  
Vol 30 (12) ◽  
pp. 6475-6484
Author(s):  
Yae Won Park ◽  
Sung Soo Ahn ◽  
Chae Jung Park ◽  
Kyunghwa Han ◽  
Eui Hyun Kim ◽  
...  

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi151-vi151
Author(s):  
Hideyuki Arita ◽  
Yuko Matsushita ◽  
Makoto Ohno ◽  
Yohei Miyake ◽  
Kuniaki Saito ◽  
...  

Abstract TERT promoter mutation is associated with 1p/19q codeletion and favorable prognosis in IDH-mutated gliomas. Prognostic and diagnostic significance of TERT promoter mutation is well-recognized in IDH-wildtype glioblastomas, but not in IDH-mutated gliomas. We investigated prognostic efficacy of TERT mutation in a cohort of 560 Japanese IDH-mutated adult gliomas. The molecular status of IDH, TERT and 1p/19q and patient clinical data including Karnofsky performance status (KPS) were collected in all cases. TERT mutations and 1p/19q codeletions were found in 303 and 285 cases, respectively. The patient cohort was divided into four groups by a combination of the 1p/19q and TERT status. The characteristics of 1p/19q intact-TERT mutated group (Astro-TERT group, n=24) were compared with those of 1p/19q intact-TERT wild (Astro-group, n=251) or 1p/19q codeleted-TERT mutated (Oligo-group, n=279) cases. Astro-TERT group with any grade showed intermediate overall survival between the Oligo-group and Astro-group although the survival differences were not statistically significant (median overall survival (OS) not reached (NR) versus NR, and 106 months, respectively. p >0.05). We further conducted subgroup analysis by adjusting KPS and WHO grade as Cox regression analysis for survival indicated the unfavorable survival impact of KPS < 90 and WHO grade IV. In the subgroup with favorable KPS (90–100) and grade II-III (n=438), The OS of Astro-TERT group (median NR) was significantly longer survival than that of Astro-group (median 120.2 months, p=0.032), and was comparable with that of the Oligo-group (median NR, p >0.05). On the other hand, OS of none of the molecular groups significantly differ in poorer KPS subgroups (p >0.05). In grade IV tumors, the OS of the Astro-TERT group (NR) was comparable with that of Astro-group (29 months, p=0.19) rather than Oligo-group (NR, p=0.051). Thus, TERT promoter status provides a valuable prognostic information for IDH-mutated grade II-III gliomas in the current molecular diagnostic system.


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