Genetic and Clinical Characteristics of Mutated Melanoma Reveal High Tumor Mutational Load without Implications on Patient Survival.

(1) Background: Melanoma has the highest mortality of all cutaneous tumors, despite recent treatment advances. Many relevant genetic events have been identified in the last decade, including recurrent mutations, which in various tumors have been associated with improved outcomes to immunotherapy. (2) Methods: Retrospective analysis of 116 melanoma samples harboring mutations. Assessment of clinical and genetic characteristics was performed as well as correlations with treatment outcome applying Kaplan-Meier (log-rank test), Fisher's exact and Chi-squared tests. (3) Results: The majority of mutations were in cutaneous and occult melanoma. mutated samples had a higher number of mutations than wild-type samples and harbored UV-mutations. A male predominance was observed. Many samples also harbored mutations. No apparent differences were noted between samples harboring genetically inactivating (frame-shift or nonsense) mutations and samples with other mutations. No differences in survival or response to immunotherapy of patients with mutant melanoma were observed. (4) Conclusions: mutations primarily occur in cutaneous melanomas with a higher mutation burden. In contrast to findings in other tumors, our data does not support mutations being a biomarker of favorable response to immunotherapies in melanoma. Larger prospective studies would still be warranted.