Differences in survival according to the pTERT mutation subtypes (-124C > T, -146C > T, and tandem -138_139CC > TT) have been observed. The present study aimed to describe the clinical as the histopathological and molecular cutaneous melanoma features according to the presence of the three most prevalent pTERT mutation subtypes (-124C > T, -146C > T, and tandem -138_139CC > TT). A retrospective cross-sectional study including 684 patients was designed, and a Partial Least-Squares Discriminant Analysis (PLS-DA) was performed. After the PSL-DA, it was observed that the tandem -138_139CC > TT subtype differs from the other subtypes. The model demonstrated that the -124C > T and the -138_139 CC > TT subtypes were associated with fast-growing melanomas (OR 0.5, CI 0.29-0.86, p = .012) and with Breslow >2 mm (OR 0.6, CI 0.37-0.97, p = .037), compared to the -146C > T mutation. Finally, the -124C > T appeared to be more associated with the presence of TILs (non-brisk) than the -146C > T (OR 0.6, CI 0.40-1.01, p = .05). These findings confirmed that the -124C > T and the tandem -138_139 CC > TT subtypes are both highly associated with the presence of features of aggressiveness; however, only the -124C > T was highly associated with TILs. This difference could explain the worse survival rate associated with the tandem -138_139CC > TT mutations.

Department of Dermatology Fundación Instituto Valenciano de Oncología Valencia Spain

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

Department of Pathological Anatomy Fundación Instituto Valenciano de Oncología Valencia Spain

Division of Functional Genome Analysis Deutsches Krebsforschüngzentrum Heidelberg Germany

Escuela de Doctorado Universidad Católica de Valencia San Vicente Mártir València Spain

Institute of Medical Biometry and Informatics University of Heidelberg Heidelberg Germany

Instituto Dermatológico Dr Alonso Hospital Vithas Valencia 9 de Octubre Spain

Laboratory of Molecular Biology Fundación Instituto Valenciano de Oncología Valencia Spain

Máster de Ingeniería de Análisis de Datos Toma de Decisiones y Mejora de Procesos Universidad Politécnica de Valencia Valencia Spain

School of Medicine Universidad Católica de Valencia San Vicente Mártir València Spain

Skin Cancer and Aging Lab Cancer Research UK Manchester Institute University of Manchester Manchester UK

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