Telomerase reverse transcriptase promoter mutations in primary cutaneous melanoma

Nat Commun. 2014 Feb 26:5:3401. doi: 10.1038/ncomms4401.


We previously reported a disease segregating causal germline mutation in a melanoma family and recurrent somatic mutations in metastasized tumours from unrelated patients in the core promoter region of the telomerase reverse transcriptase (TERT) gene. Here we show that the TERT promoter mutations, besides causing an increased gene expression, associate with increased patient age, increased Breslow thickness and tumour ulceration in 287 primary melanomas. The mutations are more frequent at both intermittently and chronically sun-exposed sites than non-exposed sites and tend to co-occur with BRAF and CDKN2A alterations. The association with parameters generally connected with poor outcome, coupled with high recurrence and mechanistic relevance, raises the possibility of the eventual use of TERT promoter mutations in the disease management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Mutational Analysis
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Promoter Regions, Genetic / genetics*
  • Proto-Oncogene Proteins B-raf / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Sunlight
  • Telomerase / genetics*


  • Cyclin-Dependent Kinase Inhibitor p16
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Telomerase