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 language | English |
|---|---|
| Pages (from-to) | 1759-1768 |
| Number of pages | 10 |
| Journal | Journal of Investigative Dermatology |
| Volume | 129 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2009 |
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ASJC Scopus subject areas
- Dermatology
- Biochemistry
- Cell Biology
- Molecular Biology
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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 journal › Article
}
TY - JOUR
T1 - Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of KIT
AU - Daniotti, Maria
AU - Ferrari, Andrea
AU - Frigerio, Simona
AU - Casieri, Paola
AU - Miselli, Francesca
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
AU - Pilotti, Silvana
AU - Rodolfo, Monica
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=67449150186&partnerID=8YFLogxK
U2 - 10.1038/jid.2008.422
DO - 10.1038/jid.2008.422
M3 - Article
C2 - 19158841
AN - SCOPUS:67449150186
VL - 129
SP - 1759
EP - 1768
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 7
ER -