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Mutated and amplified NRAS in a subset of cutaneous melanocytic lesions with dermal spitzoid morphology: report of two pediatric cases located on the ear
Author(s) -
Dubruc Estelle,
Balme Brigitte,
Dijoud Frédérique,
Disant Francois,
Thomas Luc,
Wang Qing,
Pissaloux Daniel,
de la Fouchardiere Arnaud
Publication year - 2014
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.12389
Subject(s) - neuroblastoma ras viral oncogene homolog , spitz nevus , hras , biology , pathology , congenital melanocytic nevus , blue nevus , nevus , melanoma , phenotype , mutation , medicine , cancer research , gene , genetics , kras
Extensive cytogenetic testing is slowly unveiling the complexity of the genomics of melanocytic tumors. NRAS mutations have been the first genetic abnormality described in malignant melanomas. We report the cases of two children, presenting a melanocytic lesion located on the ear. One appeared as a combined dermal clone inside a congenital nevus and the other as a centimetric purely dermal tumor. Both tumors were composed of spindled spitzoid melanocytes with atypical histologic features. aCGH and FISH revealed an amplification of the NRAS gene. Sequencing showed an exon 3 NRAS mutation. In the combined case, the amplification was limited to the spitzoid component, underscoring a possible phenotypic shift induced by the alteration. Similarly an overexpression of CyclinD1 and elevation of ki‐67 was found in the spitzoid component confirming a raise in proliferation. Such combination of mutation and copy number increase has been previously reported for the HRAS gene in a subset of Spitz nevi. Further studies must evaluate if mutated NRAS is also amplified in melanomas arising in this clinical setting. These combined alterations could represent an early event ultimately leading to malignancy.