TERT promoter mutations in melanoma survival.

Research output: Contribution to journalArticle


Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at risk primary melanoma patients. In this study we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. DNA from 300 patients with stage I/II melanoma was sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression free and melanoma specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease free and melanoma specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease free survival was 2.25 (95%CI 1.2-4.4) and for melanoma specific survival 5.8 (95%CI 1.8-18.1). The effect of the mutations on melanoma-specific survival in non-carriers of variant allele of the polymorphism was significant (HR 4.4, 95%CI 1.3-14.9) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.4, 95%CI 0.1-0.9). The data in this study provides preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter. This article is protected by copyright. All rights reserved.


  • Eduardo Nagore
  • Barbara Heidenreich
  • Sívaramakrishna Rachakonda
  • Zaida Garcia-Casado
  • Celia Requena
  • Virtudes Soriano
  • Christoph Frank
  • Victor Traves
  • Esther Quecedo
  • Josefa Sanjuan-Gimenez
  • Kari Hemminki
  • Maria Teresa Landi
  • Rajiv Kumar
External organisations
  • German Cancer Research Centre
  • Valencia Oncology Institute Foundation
  • Hospital Arnau de Vilanova in Valencia
  • National Institutes of Health, United States
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)75-84
JournalInternational Journal of Cancer
Issue number1
Early online date2016 Feb 13
Publication statusPublished - 2016
Publication categoryResearch