Analysis of the somatic mutational landscape of cutaneous melanoma across racial and ethnic groups

Summary: Abstract Body: While racial disparities have been identified in melanoma prognosis, data are lacking on somatic mutational differences between tumors from patients of different racial and ethnic backgrounds. We investigated mutation count, tumor mutational burden (TMB), copy number variations, and known driver mutation prevalence in various racial and ethnic groups by examining two independent sample sets, cutaneous melanomas of any histologic subtype (n=432) and acral melanomas (n=38), available through the cBio Cancer Genomics Portal. For melanomas of any subtype, both mean mutation count and TMB were significantly lower in tumors from Asian, Black, or Hispanic patients than in those from non-Hispanic White patients (287.1 vs 779.1 muts and 9.6 vs 27.3 mut/Mb, respectively; p<0.001). Similarly, for acral melanomas, tumors from Black patients had significantly lower mean mutation count and TMB compared to those from non-Hispanic White patients (63.4 vs 238.9 muts and 2.1 vs 7.8 mut/Mb, respectively; p<0.05). In all melanoma subtypes, a higher proportion of CDKN2A, KIT, and TERT mutations were found in tumors from non-Hispanic White patients than in those from Asian, Black, or Hispanic patients. Acral melanomas from Black patients had a higher proportion of CCND1 and NF1 mutations compared to those from White patients. Discovery of differences in TMB, unique genetic mutations, or known driver mutation prevalence in specific racial or ethnic groups may enable more personalized and effective treatment options and ultimately reduce melanoma disparities. Mohammad Saffari Doost², Marin P. Melloy^{2, 3}, Laura J. Young², John D. McPherson¹, Maija Kiuru² 1. Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, United States. 2. UC Davis Health, Sacramento, CA, United States. 3. University of Minnesota Medical School, Minneapolis, MN, United States. Pigmentation, Melanoma, and Melanoma Immune Surveillance