A group at University Hospital Essen in German confirmed the commonality of mutations in the gene for telomerase reverse transcriptase (TERT) in patients with cutaneous melanoma through a new study published in Journal of the National Cancer Institute. Authors Klaus Griewank, MD, Dirk Schadendorf, MD, and colleagues discovered a strong association among TERT promoter mutations, pathological characteristics, and prognosis of melanoma.
As described in the article, “TERT Promoter Mutation Status as an Independent Prognostic Factor in Cutaneous Melanoma,” the research team found mutations in 43% of melanoma tumors that were genetically sequenced. Of the 410 tumor samples obtained, 362 were successfully sequenced, and 154 of these had TERT promoter mutations.
Frequency of mutations was spread among melanoma subtypes, with the most frequent occurrence in patients with nonacral skin and occult primary melanomas, and the least frequent in mucosal and acral melanomas. Mutations in BRAF and NRAS, Breslow thickness, and histologic type were associated with TERT promoter mutations. Additionally, these mutations displayed UV-induced characteristics and carried a UV signature.
Finally, when prognosis was analyzed among patients, it was found nonacral cutaneous melanoma patients had poorer overall survival when they had a mutation. Median survival was only 80 months for these patients, while non-mutated patients had a median survival of 291.
Previous studies outside the research group have identified TERT mutations in other cancers, including bladder cancer, hepatocellular carcinoma, thyroid cancer, and gliomas. However, the researchers noted, “Interestingly, even looking at subgroups, we failed to find the comparably high percentages (> 70%) of TERT promoter mutations that have previously been reported in cell lines, short-term cultures, or matched metastasis.”
This intriguing aspect, as well as the potential to apply the findings in a translational setting, may motivate future studies. The authors believe, “Additional studies could further investigate whether TERT promoter mutations are of therapeutic relevance, either in terms of influencing the efficacy of established therapies or whether they might even prove to be valuable direct therapeutic targets.”