ArticleEuropean journal of cancer (Oxford, England : 1990)2022
TERT promoter mutations are associated with longer progression-free and overall survival in patients with BRAF-mutant melanoma receiving BRAF and MEK inhibitor therapy.
Article in European journal of cancer (Oxford, England : 1990), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Leptomeningeal Dissemination in TERT Promoter-mutant Anaplastic Pleomorphic Xanthoastrocytoma Responding to BRAF-MEK Inhibition: A Case Report.NMC case report journal · 2026Article
- Improved prediction of MAPKi response duration in melanoma patients using genomic data and machine learning.NPJ precision oncology · 2025Article
- pTERT mutational status is associated with survival in stage IV melanoma patients receiving first-line immune therapy.European journal of cancer (Oxford, England : 1990) · 2025Article
- BRAFThyroid research · 2025Article
- Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.Experimental hematology & oncology · 2025Review
- Coexisting RET/PTC and TERT Promoter Mutation Predict Poor Prognosis but Effective RET and MEK Targeting in Thyroid Cancer.The Journal of clinical endocrinology and metabolism · 2024Article
- BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers.Cancers · 2023Review
- Article
- Clock-like Mutation Signature May Be Prognostic for Worse Survival Than Signatures of UV Damage in Cutaneous Melanoma.Cancers · 2023Article
- TERT Expression Induces Resistance to BRAF and MEK Inhibitors in BRAF-Mutated Melanoma In Vitro.Cancers · 2023Article
- Article
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Authors and funding
28 authors at 12 institutions in 2 countries.
Funding
Abstract
backgroundAround 50% of cutaneous melanomas harbour therapeutically targetable BRAF V600 mutations. Reliable clinical biomarkers predicting duration of response to BRAF-targeted therapies are still lacking. Recent in vitro studies demonstrated that BRAF-MEK inhibitor therapy response is associated with tumour TERT promoter mutation status. We assessed this potential association in a clinical setting.
methodsThe study cohort comprised 232 patients with metastatic or unresectable BRAF V600-mutated melanoma receiving combined BRAF/MEK inhibitor treatment, including a single-centre retrospective discovery cohort (N = 120) and a prospectively collected multicenter validation cohort (N = 112). Patients were excluded if they received BRAF or MEK inhibitors in an adjuvant setting, as monotherapy, or in combination with immunotherapy. Kaplan-Meier and univariate/multivariate Cox regression analyses were performed as appropriate.
resultsmedian age at first diagnosis was 54 years (range 16-84 years). The majority of patients were men 147/232 (63.4%). Most tumours harboured TERT promoter mutations (72%, N = 167). A survival advantage was observed in both progression-free survival (PFS) and overall survival (OS) for patients with TERT promoter-mutant versus wild-type tumours in both the discovery cohort (mPFS of 9.6 months [N = 87] vs 5.0 months [N = 33]; hazard ratio [HR] = 0.56 [95% confidence interval {CI} 0.33-0.96] and mOS of 33.6 months vs 15.0 months; HR = 0.47 [95%CI 0.32-0.70]) as well as the validation cohort (mPFS of 7.3 months [N = 80] vs 5.8 months [N = 32]; HR = 0.67 [95%CI 0.41-1.10] and mOS of 51.1 months vs 15.0 months; HR = 0.33 [95%CI 0.18-0.63]). In the pooled cohort of TERT promoter-mutant (N = 167) versus wild-type (N = 65) tumours, respectively, PFS was 8.9 versus 5.5 months, (HR = 0.62; 95%CI 0.45-0.87; P = 0.004), and OS was 33.6 versus 17.0 months, (HR = 0.51; 95%CI 0.35-0.75, P = 0.0001).
conclusionsIn patients with melanoma receiving BRAF/MEK-targeted therapies, TERT promoter mutations are associated with longer survival. If validated in larger studies, TERT promoter mutation status should be included as a predictive biomarker in treatment algorithms for advanced melanoma.
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