Impact of methylation and mutation modifications on melanoma progression through evaluation of paired primary and secondary lesions from same patients

Cutaneous melanoma is a complex disease whose progression is driven by alterations in both gene pathways and epigenetic mechanisms that may continue to evolve through the disease course. Among epigenetic alterations, gene methylation has been reported to play an important role in dysregulation of the host immune system into the tumour microenvironment, contributing to foster immune evasion. We investigated distribution of mutations in all main gene involved in tumorigenesis and methylation profiles among primary and paired metastatic melanoma tissues (N=76) from same patients, also exploring the correlation between methylation classes and clinical outcome. A significant decrease in both tumour mutation load and methylation level after progression to metastasis was found; a trend toward longer survival was observed for intermediate methylation classes.