Distribution of TERT promoter mutations in primary and metastatic melanomas in Austrian patients
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TERT promoter mutations were detected at high frequencies in several cancer types including melanoma. Previous reports showed that these recurrent mutations increase TERT gene expression and the use of TERT mutation status as prognostic factor was suggested.
Here we screen a panel of 115 melanoma tumor samples from Austrian patients to evaluate the prevalence and distribution of TERT promoter mutations. The association with clinical and tumor characteristics and the effect on overall survival was analyzed.
Genomic DNA from formalin-fixed paraffin-embedded tumor samples was isolated followed by PCR amplification, Sanger sequencing and statistical analysis.
We identified TERT promoter mutations in 63 of 115 (54.8%) tumor samples. No statistical significant difference in mutation frequency between primary (22/40 [55%]) and metastatic lesions (41/75 [54.7%]) was detected. BRAF-/NRAS-mutated tumors showed a higher frequency of TERT mutations (pT OR 2.24, 95% CI 0.56–9.02, p = 0.3) (met OR 2.74, 95% CI 0.98–7.66, p = 0.05). In primary melanoma, the presence of alterations in TERT was associated with the carrier status of a common single-nucleotide polymorphism rs2853669 (OR 4.55, CI 1.18–17.52, p = 0.03). In this patient cohort, TERT promoter mutations were not associated with clinical characteristics such as the presence of ulceration or Breslow thickness or showed an effect on overall survival.
Alterations in the TERT promoter region are one of the most frequent mutations in melanoma. Based on this analysis and preliminary evidence, prospective studies will be needed to evaluate the reliability of TERT promoter mutations as prognostic factors in melanoma.
KeywordsMelanoma TERT promotor mutation Primary tumor Metastatic lesion
We thank Lorenzo Cerroni and Isabella Fried (Department of General Dermatology, Medical University Graz, Graz, Austria) for supporting this study and Gerlinde Mayer and Ulrike Schmidbauer (Department of General Dermatology, Medical University Graz, Graz, Austria) for excellent technical assistance.
This study was funded by the FWF graduate school DK MOLIN.
Compliance with ethical standards
Conflict of interest
The authors RO, CR, BH, RK and DS state no conflict of interest. Author SU has received a honorarium from Roche for attending an advisory board. Author JCB has received speaker honorariums from Amgen, MerckSerono and Pfizer, advisory board honorariums from Amgen, MerckSerono, MSD, Novartis and Takeda as well as research funding from Boehringer Ingelheim, BMS and MerckSerono; none of these activities are related to the submitted report.
The study was approved by the institutional review board of the Medical University of Graz (ethics votum 24-292 ex 11/12). Informed consent: Informed consent was obtained from all individual participants included in the study.