Molecular alterations in patients of color with advanced cutaneous and unknown primary melanomas

Cutaneous melanoma is rare in patients of color (POC), and the genomics are not well understood.

To describe mitogen-activated protein kinase drivers and tumor mutational burden of cutaneous and unknown primary melanoma in POC and compare them with non-Hispanic White patients.

We analyzed a retrospective convenience cohort of 676 patients with advanced cutaneous and unknown primary melanoma undergoing clinically warranted multigene sequencing with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. Self-identified (self-ID) POC were defined as non-White race and/or Hispanic ethnicity; this cohort was also analyzed by genetically inferred ancestry and skin tone using the Monk scale.

Self-ID POC (n = 35) had frequent B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutations (43%) and, compared with non-Hispanic White (N = 641) patients, more "pan-wild-type" tumors of unknown driver (14% vs 4%; P = .010). Among self-ID POC, skin tone and inferred ancestry showed moderate overlap, but did not consistently predict genomic features. Median tumor mutational burden was higher among patients with light (N = 185) than among patients with medium or dark (N = 8) skin tone (15.8 vs 2.6; P < .0001).

Skin tone assessments were only available for a subset of patients (N = 193). BRAF mutations are underestimated given molecular testing preferentially sent in patients with BRAF wild-type disease.

Cutaneous and unknown primary melanomas in self-ID POC had lower median tumor mutational burden and were more likely to be pan-wild-type, reflecting differences in pathogenesis. Larger-scale studies are needed to validate these findings.