Genetic Abnormalities in Large to Giant Congenital Nevi: Beyond NRAS Mutations
| Autor: | Martins da Silva V, Martínez-Barrios E, Tell-Martí G, Dabad M, Carrera C, Aguilera P, Daniel Antoni Brualla Palazón, Esteve-Codina A, Vicente-Villa MA, Puig S, Puig-Butillé JA, Malvehy J |
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| Rok vydání: | 2019 |
| Zdroj: | JOURNAL OF INVESTIGATIVE DERMATOLOGY r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname |
| ISSN: | 0022-202X |
| Popis: | Large and giant congenital melanocytic nevi (CMN) are rare melanocytic lesions mostly caused by postzygotic NRAS alteration. Molecular characterization is usually focused on NRAS and BRAF genes in a unique biopsy sample of the CMN. However, large/giant CMN may exhibit phenotypic differences among distinct areas, and patients differ in features such as presence of multiple CMN or spilus-like lesions. Herein, we have characterized a series of 21 large/giant CMN including patients with spilus-type nevi (9/21 patients, 42.8%). Overall, 53 fresh frozen biopsy samples corresponding to 40 phenotypically characterized areas of large/giant CMNs and 13 satellite lesions were analyzed with a multigene panel and RNA sequencing. Mutational screening showed mutations in 76.2% (16/21) of large/giant CMNs. A NRAS mutation was found in 57.1% (12/21) of patients, and mutations in other genes such as BRAF, KRAS, APC, and MET were detected in 14.3% (3/21) of patients. RNA sequencing showed the fusion transcript ZEB2-ALK and SOX5-RAF1 in large/giant CMN from two patients without missense mutations. Both alterations were not detected in unaffected skin and were detected in different areas of affected skin. These findings suggest that large/giant CMN may result from distinct molecular events in addition to NRAS mutations, including point mutations and fusion transcripts. |
| Databáze: | OpenAIRE |
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