Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of KIT

Maria Daniotti, Andrea Ferrari, Simona Frigerio, Paola Casieri, Francesca Miselli, Elisa Zucca, Paola Collini, Gabriella Della Torre, Siranoush Manoukian, Bernard Peissel, Aldo Bono, Mario Santinami, Giorgio Parmiani, Licia Rivoltini, Silvana Pilotti, Monica Rodolfo

Research output: Contribution to journalArticlepeer-review


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 (50%) in lesions from pediatric and familial patients, whereas no NRAS mutations were detected.

Original languageEnglish
Pages (from-to)1759-1768
Number of pages10
JournalJournal of Investigative Dermatology
Issue number7
Publication statusPublished - Jul 2009

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology


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