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The Genomic Landscape of Childhood and Adolescent Melanoma

Despite remarkable advances in the genomic characterization of adult melanoma, the molecular pathogenesis of pediatric melanoma remains largely unknown. We analyzed 15 conventional melanomas (CM), 3 melanomas arising in congenital nevi (CNM), and 5 spitzoid melanomas (SM), using various platforms, including whole genome or exome sequencing, molecular inversion probe assay, and/or targeted sequencing. CM demonstrated a high burden of somatic single nucleotide variations (SNV), with each case containing a TERT promoter (TERT-p) mutation, 13/15 containing an activating BRAF V600 mutation, and >80% of the identified SNV consistent with UV damage. By contrast, the 3 CNM contained an activating NRAS Q61 mutation and no TERT-p mutations. SM were characterized by chromosomal rearrangements resulting in activated kinase signaling in 40%, and an absence of TERT-p mutations except for the one SM that succumbed to hematogenous metastasis. We conclude that pediatric CM has a very similar UV-induced mutational spectrum to that found in the adult counterpart, emphasizing the need to promote sun protection practices in early life and to improve access to therapeutic agents being explored in adults in young patients. By contrast, the pathogenesis of CNM appears to be distinct. TERT-p mutations may identify the rare subset of spitzoid melanocytic lesions prone to disseminate.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001001032 Illumina HiSeq 2000 12
EGAD00001001246 Illumina HiSeq 2000 28
EGAD00001001247 Illumina HiSeq 2000 7
EGAD00001001432 Illumina HiSeq 2000 1337
Publications Citations
The genomic landscape of childhood and adolescent melanoma.
J Invest Dermatol 135: 2015 816-823
Genomic analysis and clinical management of adolescent cutaneous melanoma.
Pigment Cell Melanoma Res 30: 2017 307-316