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 journalArticle

43 Citations (Scopus)

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 (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
Volume129
Issue number7
DOIs
Publication statusPublished - Jul 2009

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Pediatrics
Melanoma
Skin
Genes
Germ Cells
Mutation
p16 Genes
Fluorescence
Rare Diseases
Fluorescence In Situ Hybridization
Immunohistochemistry
Control Groups
Proteins
Incidence

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of KIT. / Daniotti, Maria; Ferrari, Andrea; Frigerio, Simona; Casieri, Paola; Miselli, Francesca; Zucca, Elisa; Collini, Paola; Della Torre, Gabriella; Manoukian, Siranoush; Peissel, Bernard; Bono, Aldo; Santinami, Mario; Parmiani, Giorgio; Rivoltini, Licia; Pilotti, Silvana; Rodolfo, Monica.

In: Journal of Investigative Dermatology, Vol. 129, No. 7, 07.2009, p. 1759-1768.

Research output: Contribution to journalArticle

Daniotti, Maria ; Ferrari, Andrea ; Frigerio, Simona ; Casieri, Paola ; Miselli, Francesca ; Zucca, Elisa ; Collini, Paola ; Della Torre, Gabriella ; Manoukian, Siranoush ; Peissel, Bernard ; Bono, Aldo ; Santinami, Mario ; Parmiani, Giorgio ; Rivoltini, Licia ; Pilotti, Silvana ; Rodolfo, Monica. / Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of KIT. In: Journal of Investigative Dermatology. 2009 ; Vol. 129, No. 7. pp. 1759-1768.
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AU - Zucca, Elisa

AU - Collini, Paola

AU - Della Torre, Gabriella

AU - Manoukian, Siranoush

AU - Peissel, Bernard

AU - Bono, Aldo

AU - Santinami, Mario

AU - Parmiani, Giorgio

AU - Rivoltini, Licia

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