Clinical and genetic characteristics of -mutated non-uveal and uveal melanoma.

BACKGROUND

Screening for gene mutations has become routine clinical practice across numerous tumor entities, including melanoma. gene mutations have been identified in various tumor types and acknowledged as a critical event in metastatic uveal melanoma, but their role in non-uveal melanoma remains inadequately characterized.

METHODS

A retrospective analysis of all melanomas sequenced in our department from 2014-2022 (n=2650) was conducted to identify mutated samples. Assessment of clinical and genetic characteristics was performed as well as correlations with treatment outcome.

RESULTS

mutations were identified in 129 cases and distributed across the entire gene without any apparent hot spots. Inactivating mutations were more prevalent in uveal (55%) compared to non-uveal (17%) melanomas. Non-uveal mutated melanomas frequently exhibited UV-signature mutations and had a significantly higher mutation load than uveal melanomas. and mutations were common in uveal melanomas, while MAP-Kinase mutations were frequent in non-uveal melanomas with , V600 and Q61 mutations occurring in decreasing frequency, consistent with a strong UV association. Survival outcomes did not differ among non-uveal melanoma patients based on whether they received targeted or immune checkpoint therapy, or if their tumors harbored inactivating mutations.

CONCLUSION

In contrast to uveal melanomas, where mutations serve as a significant prognostic indicator of an unfavorable outcome, mutations in non-uveal melanomas are primarily considered passenger mutations and do not appear to be relevant from a prognostic or therapeutic perspective.