title: Genomic analysis and clinical management of adolescent cutaneous melanoma.
abstract: Melanoma in young children is rare; however, its incidence in adolescents and young adults is rising. We describe the clinical course of a 15-year-old female diagnosed with AJCC stage IB non-ulcerated primary melanoma, who died from metastatic disease 4 years after diagnosis despite three lines of modern systemic therapy. We also present the complete genomic profile of her tumour and compare this to a further series of 13 adolescent melanomas and 275 adult cutaneous melanomas. A somatic BRAFV600Emutation and a high mutational load equivalent to that found in adult melanoma and composed primarily of C>T mutations were observed. A germline genomic analysis alongside a series of 23 children and adolescents with melanoma revealed no mutations in known germline melanoma-predisposing genes. Adolescent melanomas appear to have genomes that are as complex as those arising in adulthood and their clinical course can, as with adults, be unpredictable.
authors.affiliation: Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.|Department of Oncology, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK.
authors.forename: Roy
authors.identifier: 0000-0002-9195-5659
authors.initials: R
authors.lastname: Rabbie
authors.affiliation: Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
authors.forename: Mamunur
authors.initials: M
authors.lastname: Rashid
authors.affiliation: Department of Medical Oncology and Targeted Therapeutics in Solid Tumors Group (IDIBAPS), Hospital Clınic de Barcelona, Barcelona, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Arance
authors.affiliation: Melanoma Unit, Radiology Service, Hospital Clınic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Sánchez
authors.affiliation: Melanoma Unit, Department of Dermatology, Hospital Clınic de Barcelona, Barcelona, Spain.|Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Tell-Marti
authors.affiliation: Melanoma Unit, Department of Dermatology, Hospital Clınic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Potrony
authors.affiliation: Melanoma Unit, Radiotherapy Oncology, Hospital Clınic, IDIBAPS, Barcelona University, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Conill
authors.affiliation: Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Remco
authors.initials: R
authors.lastname: van Doorn
authors.affiliation: Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dentro
authors.affiliation: Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Nelleke A
authors.initials: NA
authors.lastname: Gruis
authors.affiliation: Department of Oncology, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK.
authors.forename: Pippa
authors.initials: P
authors.lastname: Corrie
authors.affiliation: Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
authors.forename: Vivek
authors.initials: V
authors.lastname: Iyer
authors.affiliation: Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.|Laboratorio Internacional de Investigacion sobre el Genoma Humano, Universidad Nacional Autonoma de Mexico, Santiago de Queretaro, Mexico.
authors.forename: Carla Daniela
authors.identifier: 0000-0003-3277-7466
authors.initials: CD
authors.lastname: Robles-Espinoza
authors.affiliation: Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain.|Biochemistry and Molecular Genetics Department, Melanoma Unit, Hospital Clinic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Joan A
authors.initials: JA
authors.lastname: Puig-Butille
authors.affiliation: Melanoma Unit, Department of Dermatology, Hospital Clınic de Barcelona, Barcelona, Spain.|Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
authors.affiliation: Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
authors.forename: David J
authors.identifier: 0000-0001-9490-0306
authors.initials: DJ
authors.lastname: Adams
mesh_terms: D000293:Adolescent; D005260:Female; D023281:Genomics; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D000072078:Positron Emission Tomography Computed Tomography; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D000096142:Cutaneous Malignant Melanoma
keywords: BRAF mutation; adolescent melanoma; germline mutation; immunotherapy; ultraviolet radiation