Age‐related next‐generation sequencing mutational analysis in 1196 melanomas

Abstract

AbstractBackground and ObjectivesMelanoma mutational burden is high and approximately 50% have oncogenic mutations inBRAF. We sought to evaluate age‐related mutational differences in melanoma.MethodsWe analyzed melanoma samples in the Genomics Evidence Neoplasia Information Exchange database. Targetable mutations were identified using the Precision Oncology Knowledge Base (OncoKB).ResultsWe found 1194 patients with a common set of 30 genes. The top mutated genes in patients <40 years old (y/o) (n = 98) wereBRAF(59%),TP53(31%),NRAS(17%), andPTEN(14%); in 40–59 y/o (n = 354) wereBRAF(51%),NRAS(30%),TP53(26%), andAPC(13%); and in ≥60 y/o (n = 742) wereBRAF(38%),NRAS(33%),TP53(26%), andKDR(19%).BRAFmutations were almost mutually exclusive fromNRASmutations in <40 y/o (58/59). Mutational burden increased with age, with means of 2.39, 2.92, and 3.67 mutations per sample in patients <40, 40–59, and ≥60 y/o, respectively (p < 0.0001). There were 10 targetable mutations meeting OncoKB criteria for melanoma:BRAF(level 1),RET(level 1),KIT(level 2),NRAS(level 3A),TP53(level 3A), andFGFR2,MET,PTEN,PIK3CA, andKRAS(level 4).ConclusionsMutations in melanoma have age‐related differences and demonstrates potential targetable mutations for personalized therapies.