PATH-19. TERT PROMOTER MUTATION, NOT H3K27M MUTATION IS A PROGNOSTIC FACTOR FOR ADULT THALAMIC GLIOMAS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi118-vi119
Author(s):  
Masayuki Nitta ◽  
Yoshihiro Muragaki ◽  
Takashi Komori ◽  
kenta Masui ◽  
Taiichi Saito ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Tumor Resection ◽  
Pathological Diagnosis ◽  
Diffuse Glioma ◽  
Idh Mutation ◽  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Who Grade ◽  
Tert Promoter ◽  
H3k27m Mutation

Abstract Purpose Thalamic diffuse glioma is classified as WHO grade 4 as Diffuse midline glioma, H3K27M mutation if H3K27M mutation was found regardless of its histological findings, but the significance of H3K27M mutation is not clear compared with pediatric cases. We aimed to find genetic prognostic factors in adult thalamic diffuse gliomas. METHODS Pathological diagnosis, genetic abnormalities, and clinical course of adult newly diagnosed thalamic gliomas diagnosed and treated at our institution from July 2007 to March 2020 were retrospectively analyzed. RESULTS The number of cases was 41 (24 males, 17 females), median age was 47 years (20-75 years). Tumor localization was 20 cases on the left, 14 cases on the right, and 7 cases on both sides. The pathological diagnosis was GBM 15 cases, DMG 15 cases, AA-IDH WT 7 cases, DA-IDH WT 4 cases, all of which were IDH wild type, and none of them had IDH mutation and 1p/19q co-deletion. H3K27M mutations were found in 15 cases and TERT promoter mutations were found in 12 cases, both of which were completely mutually exclusive. Tumor resection and biopsy was performed in 33 and 8 cases, respectively, and the median removal rate was 95% for those who underwent tumor resection. The median PFS and OS of all cases were 14.3 months and 38 months, respectively, and the median OS by pathological diagnosis was GBM 12.4 months, DMG 47.4 months, AA-IDH WT 37.3 months, DA-IDH WT not reached. The median OS in the H3K27M mutant group (47.4 months) was significantly better (p=0.02) than that in the TERT promoter mutation group (13.5 months). CONCLUSION There was no IDH mutation in adult thalamic gliomas, the H3K27M mutation and the TERT promoter mutation were mutually exclusive. The H3K27M mutation was not a prognostic factor, but the TERT promoter mutation was the strongest prognostic factor.

Clinical, radiologic & prognostic profile of IDH wild type diffuse astrocytic glioma with molecular features of glioblastoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2557-2557
Author(s):  
Oluwatosin Akintola ◽  
Wesley Samore ◽  
Maria Martinez-Lage Alvarez ◽  
Elizabeth Robins Gerstner
Keyword(s):  
Clinical Trials ◽  
Methylation Status ◽  
Diffuse Astrocytoma ◽  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Who Grade ◽  
Egfr Amplification ◽  
Astrocytic Glioma ◽  
Molecular Features ◽  
Tert Promoter

2557 Background: In 2018, The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) recommended that IDH-wildtype diffuse astrocytic glioma Grade II/III with either EGFR amplification, combined whole chromosome 7 gain and whole chromosome 10 loss (+7/−10), or TERT promoter mutation should receive an integrated histological and molecular grade classification: Diffuse astrocytic glioma, IDH-wildtype with molecular features of glioblastoma, WHO grade IV. The natural history, radiologic characteristics and standard management for these patients has not been well described. They are typically excluded from clinical trials for WHO Grade IV gliomas. Methods: Adults diagnosed at Massachusetts General Hospital with IDH wildtype diffuse astrocytoma and EGFR amplification or TERT promoter mutation from 2011-2019 were identified. Demographics, functional status, radiologic features, MGMT promoter methylation status, time to progression, and overall survival were collected retrospectively. Qualitative MRI data was analyzed using the VASARI feature set. Response assessment was performed using the RANO criteria. Results: 50 patients were identified (table). 37/50 patients received standard Stupp protocol, 2/50 received hypofractionated radiotherapy with temozolomide, 6/50 received radiotherapy alone, and 1 patient received a MEK inhibitor. None were enrolled in clinical trials at diagnosis. mPFS was 10 months in the 47/50 with confirmed progression and mOS in the patients with confirmed deaths (40/50) was 17.5 months (4-47). 9/50 patients are alive with survival ranging 6-52 months. Conclusions: Outcomes for patients with molecularly defined GBM were variable. Analysis of the cohort to characterize factors that led to the observed variability is in progress. More studies on molecularly defined glioblastomas are required to better understand their behavior and to provide guidance for their inclusion or exclusion in clinical trials. [Table: see text]

scholarly journals TERT Promoter Mutation Status as an Independent Prognostic Factor in Cutaneous Melanoma

2014 ◽  
Vol 106 (9) ◽  
Author(s):  
Klaus G. Griewank ◽  
Rajmohan Murali ◽  
Joan Anton Puig-Butille ◽  
Bastian Schilling ◽  
Elisabeth Livingstone ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Cutaneous Melanoma ◽  
Independent Prognostic Factor ◽  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Mutation Status ◽  
Tert Promoter

TERT promoter mutation is associated with worse prognosis in WHO grade II and III meningiomas

2018 ◽  
Vol 139 (3) ◽  
pp. 671-678 ◽  
Author(s):  
Annamaria Biczok ◽  
Theo Kraus ◽  
Bogdana Suchorska ◽  
Nicole A. Terpolilli ◽  
Jun Thorsteinsdottir ◽  
...  
Keyword(s):  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Who Grade ◽  
Tert Promoter ◽  
Grade Ii ◽  
Worse Prognosis

scholarly journals P06.19 TERT promoter mutation is an independent prognostic factor in 1p/19q co-deleted oligodendrogliomas: a POLA network study

2016 ◽  
Vol 18 (suppl_4) ◽  
pp. iv32-iv33
Author(s):  
A. Alentorn ◽  
C. Carpentier ◽  
K. Labreche ◽  
F. Ducray ◽  
C. Dehais ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Independent Prognostic Factor ◽  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Tert Promoter

scholarly journals TB-06 Eribulin prolongs survival in an orthotopic xenograft mouse model of malignant meningioma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii7-ii7
Author(s):  
Tomoyuki Nakano ◽  
Kenji Fujimoto ◽  
Takamune Achiha ◽  
Hideyuki Arita ◽  
Mami Yasukawa ◽  
...  
Keyword(s):  
Cell Lines ◽  
Intraperitoneal Administration ◽  
Tert Promoter Mutation ◽  
Malignant Meningioma ◽  
Promoter Mutation ◽  
Who Grade ◽  
Orthotopic Xenograft ◽  
Tert Promoter ◽  
Meningioma Cell

Abstract Meningioma is the most common intracranial tumor, and its prognosis is typically favorable. However, patients of malignant meningioma (WHO grade III) most often experience recurrence, undergo multiple surgical treatments, and have poor prognosis. No effective therapy for malignant meningioma has been established yet. We recently reported an efficacy of eribulin (Haraven®) for glioblastoma. Eribulin is considered to target TERT, which is frequently mutated in its promoter. Since TERT promoter mutation is also found in malignant meningioma, this study aims at investigating the anti-tumor effect of eribulin against TERT promoter mutation-harboring human malignant meningioma cell lines in vitro and in vivo. Two meningioma cell lines IOMM-Lee and HKBMM were used in this study. In the viability assay and the flow cytometry, eribulin strongly inhibited cell proliferation by cell cycle arrest. Apoptotic cell death in malignant meningioma cell lines was confirmed by vital dye assay and immunoblotting. Moreover, wound healing assay revealed the suppression of tumor cell migration after eribulin exposure. To assess the effect of eribulin in vivo, orthotopic xenograft mouse models of both malignant meningioma cell lines were constructed. The intraperitoneal administration of eribulin significantly prolonged the survival of meningioma cell lines implanted in the brain (p<0.0001). Furthermore, apoptosis was histologically observed in brain tumor tissue by immunohistochemistry. Thus, this study suggests that eribulin is a potential therapeutic agent for treating malignant meningioma.

scholarly journals Prediction of Lower Grade Insular Glioma Molecular Pathology Using Diffusion Tensor Imaging Metric-Based Histogram Parameters

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhenxing Huang ◽  
Changyu Lu ◽  
Gen Li ◽  
Zhenye Li ◽  
Shengjun Sun ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Molecular Pathology ◽  
Diffusion Tensor ◽  
Lower Grade ◽  
Idh Mutation ◽  
Tert Promoter Mutation ◽  
Mgmt Methylation ◽  
Promoter Mutation ◽  
Tert Promoter ◽  
The Mean

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.

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