title: Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of KIT.
abstract: Childhood cutaneous melanoma is a rare disease with increasing incidence. It is not clear whether it differs from adult melanoma in etiology and clinical evolution. To genetically characterize childhood melanoma, 21 pediatric patients were studied by germ-line analysis of CDKN2A, CDK4, and MC1R genes. In addition, alterations in CDKN2A, c-Kit, BRAF, and NRAS genes were evaluated at the somatic level by direct gene sequencing, fluorescence in situ hybridization analysis, and immunohistochemistry. As a control group of susceptible patients, we studied patients from 23 melanoma-prone families. At the germ-line level, CDKN2A and MC1R gene variants were detected in 2/21 and 12/21 pediatric patients and in 9/23 and 19/22 in familial patients. At the somatic level, most lesions (9/14) from pediatric patients showed CDKN2A locus homozygous deletions and a null p16 immunophenotype, whereas most lesions (5/8) from familial patients were disomic and immunoreactive. A c-Kit low-polysomy profile seems to parallel CDKN2A homozygous deletions in pediatric melanoma whereas the single activating mutation observed segregates with familial patients. Loss of KIT protein expression was frequent (7/14) in pediatric melanomas, where metastatic cases were prevalent. BRAF(V600E) mutation occurred at a similar rate (approximately 50%) in lesions from pediatric and familial patients, whereas no NRAS mutations were detected.
authors.affiliation: Melanoma Genetics, Department of Experimental Oncology, Immunotherapy of Human Tumors Unit, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Daniotti
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.forename: Simona
authors.initials: S
authors.lastname: Frigerio
authors.forename: Paola
authors.initials: P
authors.lastname: Casieri
authors.forename: Francesca
authors.initials: F
authors.lastname: Miselli
authors.forename: Elisa
authors.initials: E
authors.lastname: Zucca
authors.forename: Paola
authors.initials: P
authors.lastname: Collini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Della Torre
authors.forename: Siranoush
authors.initials: S
authors.lastname: Manoukian
authors.forename: Bernard
authors.initials: B
authors.lastname: Peissel
authors.forename: Aldo
authors.initials: A
authors.lastname: Bono
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
authors.forename: Giorgio
authors.initials: G
authors.lastname: Parmiani
authors.forename: Licia
authors.initials: L
authors.lastname: Rivoltini
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Monica
authors.initials: M
authors.lastname: Rodolfo
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D019683:Penetrance; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins