The genomic landscape of childhood and adolescent melanoma

Charles Lu, Jinghui Zhang, Panduka Nagahawatte, John Easton, Seungjae Lee, Zhifa Liu, Li Ding, Matthew A. Wyczalkowski, Marcus Valentine, Fariba Navid, Heather Mulder, Ruth G. Tatevossian, James Dalton, James Davenport, Zhirong Yin, Michael Edmonson, Michael Rusch, Gang Wu, Yongjin Li, Matthew ParkerErin Hedlund, Sheila Shurtleff, Susana Raimondi, Vadodaria Bhavin, Yergeau Donald, Elaine R. Mardis, Richard K. Wilson, William E. Evans, David W. Ellison, Stanley Pounds, Michael Dyer, James R. Downing, Alberto Pappo, Armita Bahrami

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)816-823
Number of pages8
JournalJournal of Investigative Dermatology
Volume135
Issue number3
DOIs
StatePublished - Mar 12 2015

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    Lu, C., Zhang, J., Nagahawatte, P., Easton, J., Lee, S., Liu, Z., Ding, L., Wyczalkowski, M. A., Valentine, M., Navid, F., Mulder, H., Tatevossian, R. G., Dalton, J., Davenport, J., Yin, Z., Edmonson, M., Rusch, M., Wu, G., Li, Y., ... Bahrami, A. (2015). The genomic landscape of childhood and adolescent melanoma. Journal of Investigative Dermatology, 135(3), 816-823. https://doi.org/10.1038/jid.2014.425