Key Findings
- Molecular profiling of 8,872 melanomas by Caris revealed significant ancestry-linked differences in UV-related COSMIC mutational signatures, with SBS7a and SBS7b enriched in patients of European ancestry.
- Among melanoma patients treated with first-line immune checkpoint inhibitors (ICI), SBS7a positivity was associated with improved overall survival and time to next treatment after ICI independent of TMB.
- SBS7a was largely absent in non-UV-driven cancers and did not predict immunotherapy outcomes in uveal melanoma or renal cell carcinoma, supporting its specificity as a UV-associated prognostic biomarker.
- This study shows how large-scale genomic profiling and ancestry-informed analyses can identify biologically distinct tumor subgroups and support development of immunotherapy biomarkers.