The genomic landscape of childhood and adolescent melanoma

J Invest Dermatol. 2015 Mar;135(3):816-823. doi: 10.1038/jid.2014.425. Epub 2014 Sep 30.


Despite remarkable advances in the genomic characterization of adult melanoma, the molecular pathogenesis of pediatric melanoma remains largely unknown. We analyzed 15 conventional melanomas (CMs), 3 melanomas arising in congenital nevi (CNMs), and 5 spitzoid melanomas (SMs), using various platforms, including whole genome or exome sequencing, the molecular inversion probe assay, and/or targeted sequencing. CMs demonstrated a high burden of somatic single-nucleotide variations (SNVs), with each case containing a TERT promoter (TERT-p) mutation, 13/15 containing an activating BRAF V600 mutation, and >80% of the identified SNVs consistent with UV damage. In contrast, the three CNMs contained an activating NRAS Q61 mutation and no TERT-p mutations. SMs 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. In contrast, the pathogenesis of CNM appears to be distinct. TERT-p mutations may identify the rare subset of spitzoid melanocytic lesions prone to disseminate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Follow-Up Studies
  • GTP Phosphohydrolases / genetics*
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Melanoma / genetics*
  • Melanoma / pathology
  • Membrane Proteins / genetics*
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / pathology
  • Nevus, Epithelioid and Spindle Cell / genetics
  • Nevus, Epithelioid and Spindle Cell / pathology
  • Nevus, Pigmented / genetics
  • Nevus, Pigmented / pathology
  • PTEN Phosphohydrolase / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Telomerase / genetics*
  • Ultraviolet Rays / adverse effects
  • Young Adult


  • Membrane Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • TERT protein, human
  • Telomerase
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • GTP Phosphohydrolases
  • NRAS protein, human