Genomic profiling and therapeutic targets of Thai melanoma revealed by next-generation sequencing.

Genetic alterations represent key therapeutic targets in melanoma, but genomic profiles differ across ethnic groups and remain poorly defined in Thai patients. We characterized the somatic landscape of 33 melanoma samples (13 cutaneous, 13 acral, 7 mucosal) using the 501-gene OCA-Plus panel with next-generation sequencing, integrating clinical and genomic features. The somatic landscape revealed BRAF as the most frequently mutated gene, primarily involving the V600E variant, followed by KIT. Both BRAF and KIT emerged as significant drivers and exhibited mutual exclusivity, with BRAF mutations clustering specifically in cutaneous melanoma. Given the limited cohort size and heterogeneity, cross-ethnic comparisons of major mutational drivers revealed no statistically significant differences, necessitating further large-scale validation. Mutations in the RAS-MAPK and NOTCH oncogenic signaling pathways were the most frequent, and co-occurring alterations in MYC and Cell Cycle pathways were observed. Putative clinically actionable variants-primarily in BRAF, KIT, and NRAS-were present in 48.5% of patients, occurring most frequently in cutaneous melanoma. Notably, patients harboring KIT mutations showed a trend toward shorter disease-free survival, suggesting a potential prognostic role that warrants further investigation. These findings provide initial genomic understanding of Thai melanoma and highlight candidate actionable mutations for future precision oncology research.