Clinical implications of TERT promoter mutation on IDH mutation and MGMT promoter methylation in diffuse gliomas.

IDH mutation and MGMT promoter methylation are reliable prognostic and predictive biomarkers in grade II-IV diffuse gliomas. Recurrent mutations in the promoter region of the telomerase reverse transcriptase (TERTp) gene have also been found in diffuse gliomas. However, the prognostic and predictive effects of TERTp mutation on IDH or MGMT status are largely unknown. IDH1/2 and TERTp mutations, as well as MGMT methylation statuses, were examined via peptide nucleic acid-mediated PCR clamping and MGMT methylation-specific PCR in 67 paraffinized tumor samples, respectively. TERTp mutation was associated with older patients (≥60 years) and frontally located gliomas. Old age, frontal location, and grade IV were found to be predictive factors of TERTp mutation. TERTp mutation resulted in poor prognosis in overall diffuse gliomas. TERTp mutation was not correlated with overall survival (OS) or progression-free survival (PFS) in the diffuse gliomas. However, TERTp mutations, in combination with MGMT methylation or IDH mutation, showed that there were statistical significant survival differences between MGMT-unmethylated/TERTp-mutated and MGMT-unmethylated/TERTp-wildtype subgroups in grade II gliomas. There was a statistical significant survival difference of OS between IDH-wildtype/TERTp-mutated and IDH-mutated/TERTp-mutated subgroups in grade III gliomas. No significant associations between survival and MGMT/TERTp or IDH/TERTp status were found in grade IV gliomas. In conclusion, the combination of TERTp with IDH or MGMT status may be a prognostic indicator depending on grades.

Kim HS ，Kwon MJ ，Song JH ，Kim ES ，Kim HY ，Min KW ... -  《-》

Clinical insights gained by refining the 2016 WHO classification of diffuse gliomas with: EGFR amplification, TERT mutations, PTEN deletion and MGMT methylation.

Brito C ，Azevedo A ，Esteves S ，Marques AR ，Martins C ，Costa I ，Mafra M ，Bravo Marques JM ，Roque L ，Pojo M ... -  《BMC CANCER》

The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas.

Lee Y ，Koh J ，Kim SI ，Won JK ，Park CK ，Choi SH ，Park SH ... -  《Acta Neuropathologica Communications》

Comparative Analysis of the Prognostic Significance of IDH,TERT, EGFR and MGMT Status in Patients with Adult Non-H3-Altered Grade 4 Gliomas: A Prospective Cohort Study.

Gliomas continue to have a dismal prognosis. A myriad of genetic alterations has been described in this subset of tumors over the last decades. The integrative interpretation of the biomarker constellation for individual patients remains unclear. This study aims to evaluate the impact of some known genetic factors as prognostic biomarkers in grade 4 gliomas. Adult non-H3-altered grade 4 gliomas who underwent maximal safe resection accompanied by adjuvant therapy were successively enrolled since January 2019 till January 2021. Patient data were documented preoperatively and during the follow-up visits. The genetic profiling of the tumors included Isocitrate Dehydrogenase (IDH)-1 and IDH-2 mutation, MGMT promoter methylation rate, EGFR gene amplification and telomerase reverse transcriptase gene promoter (TERTp) mutation. Mean Overall survival (OS) and Progression-free survival (PFS) were 14.45 ± 5.13 months (3-24 months) and 10.66 ± 4.87 months respectively. TERTp-mutant group had a significantly lower OS (10.9 vs. 15.9) and PFS (6.9 vs. 12.3) than TERTp wildtype group. In the TERT-mutant group, those with concomitant IDH wildtype tumor had higher OS and PFS, comparable to those with both TERTp and IDH wildtype tumors. In multivariate analysis, IDH mutation and TERTp wildtype status were predictive of longer OS and PFS. While IDH and absence of TERTp mutation were associated with KPS > 80 across the follow-ups, their predictive values were inferior to preoperative KPS scores. TERTp mutation and IDH-wildtype status were associated with worse OS and PFS and lower follow-up KPS score in surgically resected gliomas, while MGMT and EGFR status did not have considerable prognostic value in this study.

Alimohamadi M ，Larijani A ，Pour-Rashidi A ，Farzin M ，Ebrahimi H ，Rahmani M ，Hendi K ，Yarandi KK ，Aghajanian S ，Shirani M ... -  《-》

A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas.

Arita H ，Yamasaki K ，Matsushita Y ，Nakamura T ，Shimokawa A ，Takami H ，Tanaka S ，Mukasa A ，Shirahata M ，Shimizu S ，Suzuki K ，Saito K ，Kobayashi K ，Higuchi F ，Uzuka T ，Otani R ，Tamura K ，Sumita K ，Ohno M ，Miyakita Y ，Kagawa N ，Hashimoto N ，Hatae R ，Yoshimoto K ，Shinojima N ，Nakamura H ，Kanemura Y ，Okita Y ，Kinoshita M ，Ishibashi K ，Shofuda T ，Kodama Y ，Mori K ，Tomogane Y ，Fukai J ，Fujita K ，Terakawa Y ，Tsuyuguchi N ，Moriuchi S ，Nonaka M ，Suzuki H ，Shibuya M ，Maehara T ，Saito N ，Nagane M ，Kawahara N ，Ueki K ，Yoshimine T ，Miyaoka E ，Nishikawa R ，Komori T ，Narita Y ，Ichimura K ... -  《Acta Neuropathologica Communications》