Comprehensive genomic profiling (CGP) and tumor mutational burden (TMB) assessment in subtypes of metastatic melanoma

摘要: Background: Metastatic melanoma (MM) is widely treated with both kinase inhibitors and immunotherapies, providing meaningful survival benefit. Contrasting CGP and TMB results across MM subtypes provides a blueprint for rational decision making in light of increasing effective therapeutic options.Methods: CGP for 2,225 MM evaluated up to 315 genes plus introns of 28 genes commonly rearranged in cancer using hybrid-capture, adaptor ligation-based libraries (mean coverage> 620X). TMB was calculated from∼ 1.1 Mb of sequenced DNA. Base substitutions, insertions and deletions (short variants; SV); rearrangements; and copy number changes were assessed.Results: We evaluated 9 MM subtypes: routine cutaneous (CT), desmoplastic (DM), acral lentiginous (AL), Spitzoid (SP), gynecologic mucosal (GMC), head and neck mucosal (HN), anorectal (ARM) and ocular (OC). Each group harbored …