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Background <p>Glioblastomas (World Health Organization [WHO] grade 4) are the most lethal primary brain tumors, with a median overall survival (OS) of 12–15&#xa0;months despite multimodal treatment. MGMT promoter methylation and TERT promoter mutations are key prognostic biomarkers, but their combined utility remains incompletely defined. This study evaluated the prognostic effects of MGMT methylation, TERT mutations, and adjuvant treatment.</p> Methods <p>We retrospectively analyzed 65 patients with gliomas treated between January 2013 and December 2024, with primary analyses restricted to WHO grade 4 tumors (<i>n</i> = 54). MGMT methylation was assessed by methylation-specific PCR and TERT mutations (C228T/C250T) by Sanger sequencing. Survival was analyzed using Kaplan–Meier methods and multivariable Cox regression with bootstrap validation.</p> Results <p>In the grade 4 cohort, median OS was 12.7&#xa0;months. MGMT methylation was present in 50.0% and TERT mutations in 68.5%. MGMT methylation independently predicted improved survival (aHR 0.45, 95% CI 0.24–0.87, <i>p</i> = 0.018), while TERT mutation predicted worse survival (aHR 2.93, 95% CI 1.46–5.87, <i>p</i> = 0.003). Adjuvant chemoradiotherapy was associated with improved OS (aHR 0.44, 95% CI 0.24–0.81, <i>p</i> = 0.008). Combined stratification identified four prognostic subgroups, with MGMT-methylated/TERT-wild-type patients showing the longest survival (median OS 19.0&#xa0;months). The model demonstrated acceptable discrimination (C-index 0.697).</p> Conclusions <p>MGMT methylation and TERT mutations are independent prognostic markers in glioblastoma. This study provides real-world evidence that both biomarkers retain prognostic value after adjustment for adjuvant treatment within an internally validated model. Combined MGMT/TERT assessment provides clinically meaningful four-tier risk stratification and supports routine prognostic evaluation.</p>

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Independent associations of MGMT promoter methylation and TERT promoter mutation with overall survival in glioblastoma: a single-center retrospective cohort study

  • 期刊论文

  • 发表日期：

    2026年6月22日

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  • Akın Cengiz,
  • Serhat Yıldızhan,
  • Usame Rakip,
  • İhsan Canbek,
  • Mehmet Gazi Boyacı,
  • Semiha Orhan,
  • Adem Aslan

摘要

Background

Glioblastomas (World Health Organization [WHO] grade 4) are the most lethal primary brain tumors, with a median overall survival (OS) of 12–15 months despite multimodal treatment. MGMT promoter methylation and TERT promoter mutations are key prognostic biomarkers, but their combined utility remains incompletely defined. This study evaluated the prognostic effects of MGMT methylation, TERT mutations, and adjuvant treatment.

Methods

We retrospectively analyzed 65 patients with gliomas treated between January 2013 and December 2024, with primary analyses restricted to WHO grade 4 tumors (n = 54). MGMT methylation was assessed by methylation-specific PCR and TERT mutations (C228T/C250T) by Sanger sequencing. Survival was analyzed using Kaplan–Meier methods and multivariable Cox regression with bootstrap validation.

Results

In the grade 4 cohort, median OS was 12.7 months. MGMT methylation was present in 50.0% and TERT mutations in 68.5%. MGMT methylation independently predicted improved survival (aHR 0.45, 95% CI 0.24–0.87, p = 0.018), while TERT mutation predicted worse survival (aHR 2.93, 95% CI 1.46–5.87, p = 0.003). Adjuvant chemoradiotherapy was associated with improved OS (aHR 0.44, 95% CI 0.24–0.81, p = 0.008). Combined stratification identified four prognostic subgroups, with MGMT-methylated/TERT-wild-type patients showing the longest survival (median OS 19.0 months). The model demonstrated acceptable discrimination (C-index 0.697).

Conclusions

MGMT methylation and TERT mutations are independent prognostic markers in glioblastoma. This study provides real-world evidence that both biomarkers retain prognostic value after adjustment for adjuvant treatment within an internally validated model. Combined MGMT/TERT assessment provides clinically meaningful four-tier risk stratification and supports routine prognostic evaluation.