TERT promoter mutational status in cutaneous melanoma: an alternative to sentinel lymph node biopsy?

Abstract

Melanomas are believed to arise from the accumulation of several genetic alterations in melanocytes, which makes the mutational status of a certain tumour a useful indicator in defining its progression phase. While BRAF mutations seem important for early carcinogenesis, mutations in the TERT promoter are related to the step towards metastisation and were found to have an independent relation with prognosis. In melanoma management, risk stratification does not depend on biomarkers, but rather on clinical evaluation and few complementary exams, like sentinel lymph node (SLN) biopsy. In this study, we aimed at verifying if TERT promoter mutations could also have an important role in classifying patients in risk categories for aggressive disease and, in this way, become effective tools in disease management. We used a series of 100 melanoma patients, comprising primary and secondary tumours, with a 47% prevalence of recurrence or metastisation. Mutational analysis was performed using PCR and Sanger sequencing. Our results demonstrate that TERT promoter mutations are significantly associated with features of worse prognosis, as well as a reduced disease-free survival. TERT mutational status seems to perform similarly to SLN biopsy in predicting recurrence and metastisation. Therefore, TERT promoter mutations can constitute effective biomarkers in cutaneous melanoma, and their integration in its management algorithm should be considered.