EGAGenomicsIllumina HiSeq 2000Otherhttps://ega-archive.org/studies/EGAS00001000901EGAEGA study EGAS00001000901DATA FILES FOR SJMEL-WGSDATA FILES FOR PCGP SJMEL RNASEQDATA FILES FOR PCGP SJMEL WXSrestrictedEGADespite 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.The genomic landscape of childhood and adolescent melanoma.Lu Charles C, Zhang Jinghui J, Nagahawatte Panduka P, Easton John J, Lee Seungjae S, Liu Zhifa Z, Ding Li L, Wyczalkowski Matthew A MA, Valentine Marcus M, Navid Fariba F, Mulder Heather H, Tatevossian Ruth G RG, Dalton James J, Davenport James J, Yin Zhirong Z, Edmonson Michael M, Rusch Michael M, Wu Gang G, Li Yongjin Y, Parker Matthew M, Hedlund Erin E, Shurtleff Sheila S, Raimondi Susana S, Bhavin Vadodaria V, Donald Yergeau Y, Mardis Elaine R ER, Wilson Richard K RK, Evans William E WE, Ellison David W DW, Pounds Stanley S, Dyer Michael M, Downing James R JR, Pappo Alberto A, Bahrami Armita AfalseThe Genomic Landscape of Childhood and Adolescent MelanomaDespite 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.2017-07-26 15:39:25EGAS00001000901960625268584EGAD00001001032EGAD00001001246EGAD00001001247EGAC00001000044