---
title: "TERT Promoter Mutations and Outcomes in Advanced Melanoma Treated with BRAF/MEK or Immune Checkpoi"
id: "pubmed-42674721"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42674721"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42674721/"
doi: "10.21873/anticanres.18351"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# TERT Promoter Mutations and Outcomes in Advanced Melanoma Treated with BRAF/MEK or Immune Checkpoi
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42674721
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42674721/)
- **DOI:** [10.21873/anticanres.18351](https://doi.org/10.21873%2Fanticanres.18351)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This single-center retrospective study evaluated the clinical impact of **TERT** promoter mutations in 159 patients with metastatic melanoma receiving first-line immune checkpoint inhibitors (ICI) or **BRAF/MEK** inhibitors. - A customized next-generation sequencing panel assessed **TERT** mutational status and co-mutations; clinical outcomes included overall survival (OS) and progression-free survival (PFS) estimated by Kaplan-Meier and compared with log-rank tests. - **TERT** promoter mutations were common, detected in 73% of cases, and frequently co-occurred with **BRAF V600** mutations (84% of **TERT**-mutant cases). - In the full cohort, **TERT** status was not associated with OS or PFS. Key outcome determinants were brain and liver metastases, elevated lactate dehydrogenase (LDH), and overall metastatic burden. - In the **BRAF V600**-mutant subgroup, exploratory analyses suggested a potential interaction between **TERT** status and first-line treatment: patients with co-occurring **BRAF/TERT** mutations had longer OS with ICI than with **BRAF/MEK** inhibitors (50.3 vs 14.6 months), while **TERT** wild-type patients showed the opposite trend (7.8 vs 20.9 months). - Similar patterns for PFS were reported, but these subgroup findings were based on small numbers and were not consistently supported in multivariable models. - The authors conclude that **TERT** promoter mutations were not independently associated with survival in metastatic melanoma; suggested treatment interactions are exploratory and require validation in prospective, well-designed studies. - The study underscores the need for additional biomarkers beyond **BRAF V600** to guide first-line therapy selection in advanced melanoma, while noting the limits of retrospective, single-center analyses.
## Clinical Analysis & Structured Key Points
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paola.marchese8@unibo.it.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-2 "Department of Medical and Surgical Sciences \(DIMEC\), Alma Mater Studiorum-University of Bologna, Bologna, Italy."), [Irene Zannini](https://pubmed.ncbi.nlm.nih.gov/?term=Zannini+I&cauthor_id=42674721)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-2 "Department of Medical and Surgical Sciences \(DIMEC\), Alma Mater Studiorum-University of Bologna, Bologna, Italy."), [Dario DE Biase](https://pubmed.ncbi.nlm.nih.gov/?term=DE+Biase+D&cauthor_id=42674721)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-3 "Department of Pharmacy and Biotechnology \(FaBiT\), University of Bologna, Bologna, Italy.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-4 "Solid Tumor Molecular Pathology Laboratory, University Hospital of Bologna IRCCS, Bologna, Italy."), [Barbara Corti](https://pubmed.ncbi.nlm.nih.gov/?term=Corti+B&cauthor_id=42674721)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-5 "Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy."), [Emi Dika](https://pubmed.ncbi.nlm.nih.gov/?term=Dika+E&cauthor_id=42674721)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-6 "Division of Dermatology, University Hospital of Bologna, Bologna, Italy.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-7 "Division of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine \(DIMES\), University of Bologna, Bologna, Italy."), [Manuela Ferracin](https://pubmed.ncbi.nlm.nih.gov/?term=Ferracin+M&cauthor_id=42674721)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-2 "Department of Medical and Surgical Sciences \(DIMEC\), Alma Mater Studiorum-University of Bologna, Bologna, Italy."), [Giorgio Durante](https://pubmed.ncbi.nlm.nih.gov/?term=Durante+G&cauthor_id=42674721)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-2 "Department of Medical and Surgical Sciences \(DIMEC\), Alma Mater Studiorum-University of Bologna, Bologna, Italy."), [Barbara Melotti](https://pubmed.ncbi.nlm.nih.gov/?term=Melotti+B&cauthor_id=42674721)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-5 "Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy."), [Giovanni Tallini](https://pubmed.ncbi.nlm.nih.gov/?term=Tallini+G&cauthor_id=42674721)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-8 "Molecular Diagnostic Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy."), [Thais Maloberti](https://pubmed.ncbi.nlm.nih.gov/?term=Maloberti+T&cauthor_id=42674721)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-4 "Solid Tumor Molecular Pathology Laboratory, University Hospital of Bologna IRCCS, Bologna, Italy."), [Francesca Comito](https://pubmed.ncbi.nlm.nih.gov/?term=Comito+F&cauthor_id=42674721)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#full-view-affiliation-5 "Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy.") Affiliations Expand ### Affiliations * 1 Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy; paola.marchese8@unibo.it. * 2 Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, Bologna, Italy. * 3 Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Bologna, Italy. * 4 Solid Tumor Molecular Pathology Laboratory, University Hospital of Bologna IRCCS, Bologna, Italy. * 5 Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy. * 6 Division of Dermatology, University Hospital of Bologna, Bologna, Italy. * 7 Division of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy. * 8 Molecular Diagnostic Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy. * PMID: **42674721** * DOI: [ 10.21873/anticanres.18351 ](https://doi.org/10.21873/anticanres.18351) Item in Clipboard # Exploring the Role of _TERT_ Promoter Mutations in Advanced Melanoma Treated With BRAF/MEK Inhibitors or Immune Checkpoint Inhibitors Paola Valeria Marchese et al. Anticancer Res. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID Anticancer Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Anticancer+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Anticancer+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42674721/) . 2026 Sep;46(9):5013-5029. doi: 10.21873/anticanres.18351. ### Authors [Paola Valeria Marchese](https://pubmed.ncbi.nlm.nih.gov/?term=Marchese+PV&cauthor_id=42674721)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-1 "Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy; paola.marchese8@unibo.it.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-2 "Department of Medical and Surgical Sciences \(DIMEC\), Alma Mater Studiorum-University of Bologna, Bologna, Italy."), [Irene Zannini](https://pubmed.ncbi.nlm.nih.gov/?term=Zannini+I&cauthor_id=42674721)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-2 "Department of Medical and Surgical Sciences \(DIMEC\), Alma Mater Studiorum-University of Bologna, Bologna, Italy."), [Dario DE Biase](https://pubmed.ncbi.nlm.nih.gov/?term=DE+Biase+D&cauthor_id=42674721)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-3 "Department of Pharmacy and Biotechnology \(FaBiT\), University of Bologna, Bologna, Italy.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-4 "Solid Tumor Molecular Pathology Laboratory, University Hospital of Bologna IRCCS, Bologna, Italy."), [Barbara Corti](https://pubmed.ncbi.nlm.nih.gov/?term=Corti+B&cauthor_id=42674721)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-5 "Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy."), [Emi Dika](https://pubmed.ncbi.nlm.nih.gov/?term=Dika+E&cauthor_id=42674721)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-6 "Division of Dermatology, University Hospital of Bologna, Bologna, Italy.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-7 "Division of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine \(DIMES\), University of Bologna, Bologna, Italy."), [Manuela Ferracin](https://pubmed.ncbi.nlm.nih.gov/?term=Ferracin+M&cauthor_id=42674721)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-2 "Department of Medical and Surgical Sciences \(DIMEC\), Alma Mater Studiorum-University of Bologna, Bologna, Italy."), [Giorgio Durante](https://pubmed.ncbi.nlm.nih.gov/?term=Durante+G&cauthor_id=42674721)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-2 "Department of Medical and Surgical Sciences \(DIMEC\), Alma Mater Studiorum-University of Bologna, Bologna, Italy."), [Barbara Melotti](https://pubmed.ncbi.nlm.nih.gov/?term=Melotti+B&cauthor_id=42674721)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-5 "Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy."), [Giovanni Tallini](https://pubmed.ncbi.nlm.nih.gov/?term=Tallini+G&cauthor_id=42674721)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-8 "Molecular Diagnostic Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy."), [Thais Maloberti](https://pubmed.ncbi.nlm.nih.gov/?term=Maloberti+T&cauthor_id=42674721)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-4 "Solid Tumor Molecular Pathology Laboratory, University Hospital of Bologna IRCCS, Bologna, Italy."), [Francesca Comito](https://pubmed.ncbi.nlm.nih.gov/?term=Comito+F&cauthor_id=42674721)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674721/#short-view-affiliation-5 "Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy.") ### Affiliations * 1 Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy; paola.marchese8@unibo.it. * 2 Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, Bologna, Italy. * 3 Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Bologna, Italy. * 4 Solid Tumor Molecular Pathology Laboratory, University Hospital of Bologna IRCCS, Bologna, Italy. * 5 Medical Oncology Unit, University Hospital of Bologna IRCCS, Bologna, Italy. * 6 Division of Dermatology, University Hospital of Bologna, Bologna, Italy. * 7 Division of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy. * 8 Molecular Diagnostic Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy. * PMID: **42674721** * DOI: [ 10.21873/anticanres.18351 ](https://doi.org/10.21873/anticanres.18351) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background/aim:** Advanced melanoma treatment remains debated, particularly in patients with B-Raf proto-oncogene serine/threonine kinase (_BRAF_) V600 mutations eligible for both immune checkpoint inhibitors (ICI) and _BRAF_ /_MEK_ inhibitors. Additional biomarkers are needed to improve treatment selection. Mutations of the telomerase reverse transcriptase (_TERT_) promoter are frequent in melanoma, although their clinical role remains unclear. **Patients and methods:** We conducted a retrospective single-center study including patients with metastatic melanoma treated with first-line ICI or _BRAF_ /_MEK_ inhibitors. _TERT_ mutational status and co-mutations were assessed using a customized next-generation sequencing panel. Overall (OS) and progression-free (PFS) survival were estimated using the Kaplan-Meier method and compared with the log-rank test. **Results:** Among 159 patients, _TERT_ mutations were detected in 73% of cases and frequently co-occurred with _BRAFV_ 600 mutations (84%). In the overall population, _TERT_ status was not associated with OS or PFS. Brain and liver metastases, lactate dehydrogenase levels, and metastatic burden were the main determinants of outcome. In the _BRAFV_ 600-mutant subgroup, exploratory analyses suggested a potential interaction between _TERT_ status and the agents used in first-line treatment. Patients with _BRAF_ /_TERT_ co-mutations showed longer OS when treated with ICI than with _BRAF_ /_MEK_ inhibitors (50.3 _vs_. 14.6 months), whereas the opposite trend was observed in patients with wild-type _TERT_ (7.8 _vs_. 20.9 months). Similar patterns were observed for PFS, although findings were based on small subgroups and not consistently supported by multivariable analyses. **Conclusion:** _TERT_ promoter mutations were not independently associated with survival outcomes in metastatic melanoma. Although exploratory findings suggest a possible interaction between _TERT_ status and treatment type, further investigation of its biological relevance in well-designed prospective studies are needed. **Keywords:** BRAF; BRAF/MEK inhibitors; MEK; TERT; immunotherapy; melanoma. Copyright © 2026 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. 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