In a recent study titled “TERT Promoter Mutation Status as an Independent Prognostic Factor in Cutaneous Melanoma”, published in the Journal of the National Cancer Institute (JNCI), a group of researchers from the University Hospital Essen in Germany observed that TERT promoter mutations were more frequent in nonacral cutaneous melanomas than in acral or mucosal melanomas. Furthermore, in patients who had nonacral melanoma, TERT promoter mutations were able to independently predict poor prognosis.
Previous studies had identified frequent mutations occurring in the promoter region of the TERT (telomerase reverse transcriptase) gene, which encodes the catalytic subunit of the telomerase holoenzyme. These mutations were especially found in families with a tendency to develop melanoma and whose members developed this type of cancer at a very young age.
Along with BRAF and NRAS mutations, recurrent TERT promoter mutations seem to be the most common genomic alterations.
In this study, Klaus Griewank, MD, and colleagues assessed the presence of TERT mutations in 410 melanoma tumor samples obtained from the Departments of Dermatology of the University Hospital Essen and the Hospital Clinic, Barcelona. In addition, peripheral blood mononuclear cells (PBMCs) from patients with cutaneous melanoma were analyzed.
The team observed that TERT promoter mutations were present in 43% of the sequenced melanoma samples, and its frequency oscillated according to melanoma subtype.
Moreover, the team found that occult primary melanomas, nonacral skin melanomas, mucosal melanomas and acral melanomas had a 48%, 50%, 23% and 19% frequency in TERT mutations, respectively.
Importantly, there seemed to be a link between TERT mutations and poorer survival among patients with nonacral cutaneous melanomas, who had a median overall survival (OS) of 80 months compared to 291 months for those who did not carry the mutation.
In their study, the authors conclude, “Analysis of independent, prospectively collected data sets will be needed to validate our findings. Additional studies could further investigate whether TERT promoter mutations are of therapeutic relevance, either in terms of influencing the efficacy of established therapies (ie, BRAF inhibitors or immunotherapies) or whether they might even prove to be valuable direct therapeutic targets.”