scholarly journals TERT promoter mutations contribute to subset prognostication of lower-grade gliomas

2014 ◽  
Vol 28 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Aden Ka-Yin Chan ◽  
Yu Yao ◽  
Zhenyu Zhang ◽  
Nellie Yuk-Fei Chung ◽  
Joseph Shu-Ming Liu ◽  
...  
Keyword(s):  
Lower Grade ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Radiological Characteristics and Natural History of Adult IDH-Wildtype Astrocytomas with TERT Promoter Mutations

Neurosurgery ◽  
2018 ◽  
Vol 85 (3) ◽  
pp. E448-E456 ◽  
Author(s):  
Cristina Izquierdo ◽  
Marc Barritault ◽  
Delphine Poncet ◽  
Stéphanie Cartalat ◽  
Bastien Joubert ◽  
...  
Keyword(s):  
Natural History ◽  
Contrast Enhancement ◽  
Slow Growth ◽  
Gliomatosis Cerebri ◽  
Lower Grade ◽  
Tert Promoter ◽  
Anaplastic Transformation ◽  
Tert Promoter Mutations ◽  
History Of ◽  
Promoter Mutations

Abstract BACKGROUND Adult IDH-wildtype astrocytomas with TERT promoter mutations (TERTp) are associated with a poor prognosis. OBJECTIVE To analyze the radiological presentation and natural history of adult IDH-wildtype astrocytomas with TERTp. METHODS We retrospectively reviewed the characteristics of 40 IDH-wildtype TERTp-mutant astrocytomas (grade II n = 19, grade III n = 21) and compared them to those of 114 IDH-mutant lower grade gliomas (LGG), of 92 IDH-wildtype TERTp-mutant glioblastomas, and of 15 IDH-wildtype TERTp-wildtype astrocytomas. RESULTS Most cases of IDH-wildtype TERTp-mutant astrocytomas occurred in patients aged >50 yr (88%) and presented as infiltrative lesions without contrast enhancement (73%) that were localized in the temporal and/or insular lobes (37.5%) or corresponded to a gliomatosis cerebri (43%). Thalamic involvement (33%) and extension to the brainstem (27%) were frequently observed, as was gyriform infiltration (33%). This radiological presentation was different from that of IDH-mutant LGG, IDH-wildtype TERTp-mutant glioblastomas, and IDH-wildtype TERTp-wildtype astrocytomas. Tumor evolution before treatment initiation was assessable in 17 cases. Ten cases demonstrated a rapid growth characterized by the apparition of a ring-like contrast enhancement and/or a median velocity of diametric expansion (VDE) ≥8 mm/yr but 7 cases displayed a slow growth (VDE <8 mm/yr) that could last several years before anaplastic transformation. Median overall survival of IDH-wildtype TERTp-mutant astrocytomas was 27 mo. CONCLUSION IDH-wildtype TERTp-mutant astrocytomas typically present as nonenhancing temporo-insular infiltrative lesions or as gliomatosis cerebri in patients aged >50 yr. In the absence of treatment, although rapid tumor growth is frequent, an initial falsely reassuring, slow growth can be observed.

scholarly journals OS10.1 Survival analysis of IDH wildtype astrocytomas with molecular features of glioblastoma, WHO grade IV

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii20-iii20 ◽  
Author(s):  
C M S Tesileanu ◽  
J A F Koekkoek ◽  
L Dirven ◽  
H J Dubbink ◽  
J M Kros ◽  
...  
Keyword(s):  
Molecular Data ◽  
Lower Grade ◽  
Who Grade ◽  
Historical Cohort ◽  
Molecular Features ◽  
Tert Promoter ◽  
Significant Difference ◽  
Tert Promoter Mutations ◽  
Grade Ii ◽  
Promoter Mutations

Abstract BACKGROUND Recently, isocitrate dehydrogenase wildtype (IDHwt) lower grade gliomas (LGGs) that have a telomerase reverse transcriptase (TERT) promoter mutation and/or gain of chromosome 7 combined with loss of chromosome 10 and/or epidermal growth factor receptor amplification have been reclassified as IDHwt astrocytomas with molecular features of glioblastoma, WHO grade IV (‘astrocytomas IDHwt, WHO IV’). Survival of these tumors meeting the criteria of these tumors is less well studied. The objective of this study is to compare the overall survival (OS) between the IDHwt astrocytomas, WHO IV and histological glioblastomas (GBMs). MATERIAL AND METHODS In this retrospective multicenter cohort study, all adult patients with a newly diagnosed IDHwt LGG (histologically WHO grade II or III) and with molecular data available were selected from the Erasmus MC and the LUMC from October 2002 to April 2019. LGG patients showing contrast enhancement with necrosis on the MRI at the time of histological diagnosis were excluded. Molecular data were determined using a diagnostic NGS panel. A historical cohort of 195 patients with IDHwt GBMs with molecular data available was used to compare OS. OS was measured from the date of the first diagnostic MR scan. RESULTS 79 IDHwt LGG patients were identified of which 62 patients had molecular features of glioblastoma (‘astrocytomas IDHwt, WHO IV’), 11 patients did not have these molecular features (‘astrocytomas IDHwt, WHO II & III’). In the remaining 6 patients the molecular data were not conclusive (astrocytomas IDHwt, WHO NOS). Patients with astrocytomas IDHwt, WHO IV were slightly older at diagnosis (median age = 57 years) than patients with GBMs IDHwt in the reference cohort or astrocytomas IDHwt, WHO II & III (respectively: median age 55 years, p=0.032 and 47 years, p=0.035). The relatively young age of our GBM IDHwt cohort reflects more extensive molecular testing in younger patients and histologically lower grade tumors. The median OS of astrocytomas IDHwt, WHO IV (23.8 months) was similar to the median OS of GBMs (19.2 months, log-rank test p=0.37). The median OS in 19 patients with only TERT promoter mutations was 16.8 months, similar to GBMs (p=0.94). CONCLUSION There is no statistically significant difference between the OS of IDHwt astrocytomas with molecular features of glioblastoma and the OS of true glioblastomas. Grade II and III IDHwt astrocytoma with molecular features of glioblastoma should be designated WHO grade IV. The presence of TERT promoter mutations alone in this histological context also qualifies for this designation.

TERT promoter mutations in progressive treatment-resistant meningiomas.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2047-2047 ◽  
Author(s):  
Tareq A. Juratli ◽  
Christian Thiede ◽  
Dietmar Krex ◽  
Priscilla Kaliopi Brastianos ◽  
Hiroaki Wakimoto ◽  
...  
Keyword(s):  
Initial Diagnosis ◽  
Lower Grade ◽  
Treatment Resistant ◽  
Mutation Status ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Gene ◽  
History Of ◽  
Promoter Mutations

2047 Background: Recurrent meningiomas often undergo a grade-progression to become atypical or malignant upon recurrence. Detailed study of progressive meningioma has been hampered by the lack of available paired specimens. Here, we sequenced the TERT promoter ( TERTp) in a large series of patients with treatment-resistant meningiomas at initial diagnosis as well as their sequential recurrences. Methods: We scored 77 meningiomas from 36 patients for TERTp mutations. All patients in this study developed recurrences during the median follow-up of 13.3 years (range 6.4 - 25.5 years) and underwent three surgeries on average (range 2-8). Additionally, we screened geographically distinct sites of all TERTp-mutant meningiomas to interrogate intratumoral heterogeneity. Results: TERTp mutations were detected in 18 tumor samples (18/77 = 23.3%) from 12 patients, but not in any of the matched blood sample DNAs, excluding germline mutations. Notably, the TERTp mutations were absent in the initial lower-grade tumor and were present in the subsequent recurrent tumors. Moreover, we observe emergent spatial heterogeneity in the form of mixed populations of recurrent tumor cells containing different mutation status of the TERT promoter gene in three cases. Patients with emergence of TERTp -mutant meningiomas had a significantly shorter overall survival than their TERTp wild-type counterparts, when measured from the time of initial diagnosis (2.4 vs 11.1 years, 95% CI 0.25-4.54 vs 9.3- 16.8 years p = 0.007). Conclusions: Our data confirm the high frequency of TERTp mutations and the emergence of TERT promoter mutation in recurrent progressive meningiomas, strongly indicating the presence of ongoing evolution impacting the natural history of these tumors. TERTp mutations are mostly associated with poor outcome. Finally, our study provides important insight into the complexity of tumor heterogeneity and has important implications for targeted therapy in treatment-resistant meningiomas.

151 TERT Promoter Mutations in Progressive Treatment-resistant Meningiomas

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 236-237
Author(s):  
Tareq A Juratli ◽  
Ganesh Shankar ◽  
Mara Koerner ◽  
Shilpa Tummala ◽  
Hiroaki Wakimoto ◽  
...  
Keyword(s):  
Initial Diagnosis ◽  
Lower Grade ◽  
Treatment Resistant ◽  
Mutation Status ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Gene ◽  
History Of ◽  
Promoter Mutations

Abstract INTRODUCTION Recurrent meningiomas often undergo a grade-progression to become atypical or malignant upon recurrence. Detailed study of progressive meningioma has been hampered by the lack of available paired specimens. Here, we sequenced the TERT promoter (TERTp) in a large series of patients with treatment-resistant meningiomas at initial diagnosis as well as their sequential recurrences. METHODS We scored 77 meningiomas from 36 patients for TERTp mutations. All patients in this study developed recurrences during the median follow-up of 13.3 years (range 6.4-25.5 years) and underwent three surgeries on average (range 2–8). Additionally, we screened geographically distinct sites of all TERTp-mutant meningiomas to interrogate intratumoral heterogeneity. RESULTS >TERTp mutations were detected in 18 tumor samples (18/77 = 23.3%) from 12 patients, but not in any of the matched blood sample DNAs, excluding germline mutations. Notably, the TERTp mutations were absent in the initial lower-grade tumor and were present in the subsequent recurrent tumors. Moreover, we observe emergent spatial heterogeneity in the form of mixed populations of recurrent tumor cells containing different mutation status of the TERT promoter gene in three cases. Patients with emergence of TERTp-mutant meningiomas had a significantly shorter overall survival than their TERTp wild-type counterparts, when measured from the time of initial diagnosis (2.4 vs 11.1 years, 95% CI 0.25-4.54 vs 9.3- 16.8 years P = 0.007). CONCLUSION Our data confirm the high frequency of TERTp mutations and the emergence of TERT promoter mutation in recurrent progressive meningiomas, strongly indicating the presence of ongoing evolution impacting the natural history of these tumors. TERTp mutations are mostly associated with poor outcome. Finally, our study provides important insight into the complexity of tumor heterogeneity and has important implications for targeted therapy in treatment-resistant meningiomas.

scholarly journals TERT PROMOTER MUTATIONS CONTRIBUTE TO PROGNOSTIC SUBGROUPS OF LOWER GRADE ASTROCYTOMAS

2014 ◽  
Vol 16 (suppl 3) ◽  
pp. iii45-iii45
Author(s):  
H. K. Ng ◽  
A. Chan ◽  
Y. Yao ◽  
D. Chan
Keyword(s):  
Lower Grade ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals IDH-wildtype lower grade diffuse gliomas: the importance of histological grade and molecular assessment for prognostic stratification

2020 ◽  
Author(s):  
Giulia Berzero ◽  
Anna Luisa Di Stefano ◽  
Susanna Ronchi ◽  
Franck Bielle ◽  
Chiara Villa ◽  
...  
Keyword(s):  
Histological Grade ◽  
Lower Grade ◽  
Who Grade ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Prognostic Stratification ◽  
Grade Ii ◽  
Definition Of ◽  
Promoter Mutations ◽  
Grade Iii

Abstract Background IDH-wildtype (IDHwt) grade II gliomas are a rare and heterogeneous entity. Survival and prognostic factors are poorly defined. Methods We searched retrospectively all patients diagnosed with diffuse WHO grade II and III gliomas at our center (1989-2020). Results Out of 517 grade II gliomas, 47 were “diffuse astrocytomas, IDHwt”. Tumors frequently had fronto-temporo-insular location (28/47, 60%) and infiltrative behavior. We found TERT promoter mutations (23/45, 51%), whole chromosome 7 gains (10/37, 27%), whole chromosome 10 losses (10/41, 24%), and EGFR amplifications (4/43, 9%) but no TP53 mutations (0/22, 0%). Median overall survival (OS) was 59 months (vs. 19 months for IDHwt grade III gliomas (p&lt; 0.0001). Twenty-nine patients (29/43, 67%) met the definition of molecular glioblastoma according to cIMPACT-NOW update3. Median OS in this subset was 42 months, which was shorter compared to patients with IDHwt grade II gliomas not meeting this definition (median OS: 57 months), but substantially longer compared to IDHwt grade III gliomas meeting the definition for molecular glioblastoma (median OS: 17 months, p&lt;0.0001). Most patients with IDHwt grade II gliomas met cIMPACT criteria because of isolated TERT promoter mutations (16/26, 62%), which were not predictive of poor outcome (median OS: 88 months). Actionable targets, including 5 gene fusions involving FGFR3, were found in 7 patients (24%). Conclusions Our findings highlight the importance of histological grading and molecular profiling for the prognostic stratification of IDHwt gliomas and suggest some caution when assimilating IDHwt grade II gliomas to molecular glioblastomas, especially those with isolated TERT promoter mutation.

scholarly journals P04.06 * TERT PROMOTER MUTATIONS CONTRIBUTE TO SUBSET PROGNOSTICATION OF LOWER GRADE GLIOMAS

2014 ◽  
Vol 16 (suppl 2) ◽  
pp. ii37-ii37
Author(s):  
A. K. Chan ◽  
Y. Yao ◽  
Z. Zhang ◽  
N. Y. Chung ◽  
K. K. Li ◽  
...  
Keyword(s):  
Lower Grade ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Prognostic significance of TERT promoter mutations in follicular cell-derived thyroid carcinomas

2014 ◽  
Author(s):  
Miguel Melo ◽  
Rocha Adriana Gaspar da ◽  
Joao Vinagre ◽  
Rui Batista ◽  
Joana Peixoto ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Follicular Cell ◽  
Thyroid Carcinomas ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

In papillary thyroid cancer TERT promoter mutations have a worst impact on outcome than BRAF mutations

2015 ◽  
Author(s):  
Marina Muzza ◽  
Carla Colombo ◽  
Maria Carla Proverbio ◽  
Stefania Rossi ◽  
Delfina Tosi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Papillary Thyroid ◽  
Braf Mutations ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations
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