TERT Promoter Mutations are Associated with Visceral Spreading in Melanoma of the Trunk

Survival predictions are currently determined on the basis of NRAS/BRAF mutations, even though TERT promoter mutations have been recently associated with a poor prognosis in stage I-II melanomas. Usually, it is not recommended to perform a mutational test on primary melanoma, as the results do not always reflect the mutational status of metastases. In particular, trunk melanomas have been reported to have an unfavourable prognosis. A series of 105 advanced melanoma patients were analysed by TERT promoter Sanger sequencing. Univariate/multivariate binarylogisticregressionmodelswereperformedusingprogressiontoavisceralsiteasthedependent variable and patient/tumour characteristics as covariates. Performance of the model was assessed in an external independent primary melanoma patients’ dataset. Male gender (odds ratio (OR), 344; 95% CI, 1.12–10.6; p = 0.031), AJCC (American Joint Committee on Cancer) classification (OR, 022; 95% CI, 0.07–0.67; p = 0.008), SLNB (Sentinel Lymph Node Biopsy) status (OR, 3.05; 95% CI, 1.06–8.78; p = 0.039) and TERT-mutated trunk lesions (OR, 3.78; 95% CI, 1.35–10.6; p = 0.011) were significantly associated with the risk of developing a visceral spreading as first site of progression usingmultivariatelogisticregressionanalysis. Theseresultswereconfirmedintheexternalvalidation controlgroup. Therefore,intrunkprimarymelanomas,duetotheirhighriskofprogressiontovisceral sites, we encourage somatic TERT mutation analysis at diagnosis to identify those patients who wouldpotentiallybenefitfromamoreintensivefollow-upprotocolandapromptinitiationoftherapy.