TERT Promoter Mutations in Glioma Prognostics

Mutations in the promoter region of the telomerase reverse transcriptase gene (TERT) constitute one of the most frequent genetic alterations in adult diffuse gliomas. By upregulating telomerase activity, these promoter variants facilitate cellular immortalisation and are strongly associated with distinct clinical trajectories. In glioblastoma and oligodendroglioma, TERT promoter mutations often coexist with other molecular hallmarks, such as IDH status and 1p/19q codeletion, yielding molecular subgroups with markedly different outcomes. In lower-grade astrocytomas, their contribution to prognosis appears more nuanced, reflecting interplay with epigenetic regulators and co-occurring alterations. The incorporation of TERT promoter status into current classification schemas has refined risk stratification, guiding treatment intensity and follow-up strategies. Across populations, these mutations emerge as independent adverse prognostic markers, particularly when present alongside unmethylated MGMT promoters. Collectively, evidence underscores the global significance of TERT promoter profiling as a practical tool for personalised management and clinical trial design in neuro-oncology.

Research from Nature Portfolio

Recent studies have defined novel molecular subgroups of glioblastoma lacking both TERT promoter and IDH alterations. Detailed genomic analyses revealed alternative mechanisms of telomere maintenance, including structural rearrangements upstream of TERT that drive telomerase activation and inactivating mutations in ATRX or SMARCAL1 that confer an ALT phenotype. These findings establish the existence of telomerase-positive and ALT-positive subtypes among IDH-wild-type glioblastomas and provide a refined framework for prognostic classification beyond canonical promoter mutations.

TERT Promoter Mutations in Glioma Prognostics publication trend

The graph below shows the total number of articles in tert promoter mutations in glioma prognostics across all publications each year (not limited to Nature Index journals).

Technical terms

TERT promoter mutation: A nucleotide change in the regulatory region upstream of the TERT gene, leading to increased telomerase expression.

IDH (isocitrate dehydrogenase): An enzyme whose mutation status distinguishes prognostic subgroups in glioma.

ALT (alternative lengthening of telomeres): A telomerase-independent mechanism of telomere maintenance involving homologous recombination.

MGMT promoter methylation: An epigenetic modification of the MGMT gene promoter that silences DNA repair activity and influences response to alkylating chemotherapy.

References

1. The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas. Acta Neuropathologica Communications (2017).
2. The Biological and Clinical Role of the Telomerase Reverse Transcriptase Gene in Glioblastoma: A Potential Therapeutic Target?. Cells (2023).
3. Mutations in IDH1 , IDH2 , and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget (2014).
4. A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas. Acta Neuropathologica Communications (2016).
5. The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma. Nature Communications (2018).
6. Prognostic Impact of TERT Promoter Mutations in Adult-Type Diffuse Gliomas Based on WHO2021 Criteria. Cancers (2024).
7. Clinical insights gained by refining the 2016 WHO classification of diffuse gliomas with: EGFR amplification, TERT mutations, PTEN deletion and MGMT methylation. BMC Cancer (2019).