Mutational landscape and tumour mutational burden in adults with malignant melanoma arising from congenital naevi

Abstract

We evaluated the genetic mutations, tumour mutational burden (TMB) and ultraviolet (UV) signature pattern in melanomas arising in congenital melanocytic naevi (CMN) in adults treated at the Dana–Farber Cancer Institute. Whereas paediatric CMN melanomas are characterized by NRAS mutations and reportedly lack BRAF and PTEN mutations, analysis showed that adult CMN melanomas contain BRAF, PTEN and TERT promotor mutations. Adult CMN melanomas showed low average TMB and an absent UV signature, suggesting lower UV damage in adult CMN melanoma than in other subtypes. Patients treated with immune checkpoint inhibition showed refractory disease progression, potentially attributable to low TMB. Findings suggest adult CMN melanoma may have distinct genetic properties from paediatric CMN melanoma and show immunotherapy resistance.