20.500.12556/DiRROS-24458 UV-radiation and MC1R germline mutations are risk factors for the development of conventional and spitzoid melanomas in children and adolescents Background: Genomic characterisation has led to an improved understanding of adult melanoma. However, the aetiology of melanoma in children is still unclear and identifying the correct diagnosis and therapeutic strategies remains challenging. Methods: Exome sequencing of matched tumour-normal pairs from 26 paediatric patients was performed to study the mutational spectrum of melanomas. The cohort was grouped into different categories: spitzoid melanoma (SM), conventional melanoma (CM), and other melanomas (OT). Findings: In all patients with CM (n = 10) germline variants associated with melanoma were found in low to moderate melanoma risk genes: in 8 patients MC1R variants, in 2 patients variants in MITF, PTEN and BRCA2. Somatic BRAF mutations were detected in 60% of CMs, homozygous deletions of CDKN2A in 20%, TERTp mutations in 30%. In the SM group (n = 12), 5 patients carried at least one MC1R variant; somatic BRAF mutations were detected in 8.3%, fusions in 25% of the cases. No SM showed a homozygous CDKN2A deletion nor a TERTp mutation. In 81.8% of the CM/SM cases the UV damage signatures SBS7 and/or DBS1 were detected. The patient with melanoma arising in giant congenital nevus (CNM) demonstrated the characteristic NRAS Q61K mutation. Interpretation: UV-radiation and MC1R germline variants are risk factors in the development of conventional and spitzoid paediatric melanomas. Paediatric CMs share genomic similarities with adult CMs while the SMs differ genetically from the CM group. Consistent genetic characterization of all paediatric melanomas will potentially lead to better subtype differentiation, treatment, and prevention in the future. paediatric melanoma exome sequencing tumour-normal sequencing rare paediatric tumours true false true Angleški jezik Ni določen Neznano 2025-11-28 14:39:32 2025-11-28 14:39:33 2025-11-29 03:56:30 0000-00-00 00:00:00 2023 0 0 Nasl. z nasl. zaslona; Opis vira z dne 7. 1. 2025; str. 1-26 Vol. 96, ǂ[article no.] ǂ104797 Oct. 2023 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 616-053.2 2352-3964 10.1016/j.ebiom.2023.104797 221264899 RAZ_Liebmann_Alexandra_2023.pdf RAZ_Liebmann_Alexandra_2023.pdf 1 FF60152174607CFD80E7BB45332A8A88 85e4161d5f5ae4482f09fb426c787832239067dacdfea0c163842cf0548a4e83 e93982ff-cc5f-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36429 https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00363-8/fulltext 0 ae0398d7-cc5f-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36428 Univerzitetni klinični center Ljubljana 0 0 0