Intratumor Heterogeneity of KIT Gene Mutations in Acral Lentiginous Melanoma

Autor(es)

Comodo-Navarro, Andreia Neves ^[1] ; Fernandes, Mariana ^[1] ; Barcelos, Denise ^[1] ; Lopes Carapeto, Fernando Cintra ^[1] ; Guimaraes, Daiane Pereira ^[1] ; Moraes, Lais de Sousa ^[2] ; Cerutti, Janete ^[2] ; Miazato Iwamura, Edna Sadayo ^[1] ; Landman, Gilles ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Patol, Rua Botucatu 740, BR-04023062 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Morfol & Genet, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF DERMATOPATHOLOGY; v. 42, n. 4, p. 265-271, APR 2020.
• Citações Web of Science: 2

Resumo

Melanoma is an aggressive skin malignancy, and the acral lentiginous melanoma (ALM) subtype affects non-sun-exposed sites such as the volar surface of the hands and feet and the subungual region and is most common in Asians, Hispanics, and Afro-descendants. The presence of different clones within the same tumor seems to influence the aggressiveness of tumors. Patients with mutations in the KIT gene have shown a good response to tyrosine kinase inhibitor therapy. We tested the hypothesis of intratumor heterogeneity through analysis of KIT gene mutations in ALM and determined the correlation between KIT mutations and demographic, clinical, and histopathological variables. Twenty-five ALM samples were examined. We selected up to four different regions per tumor for sequencing by the Sanger method for analysis of KIT gene exon 11 and exon 13 mutations. Advanced lesions were predominant, and the main histopathological characteristics of lesions were Breslow index >4.0 mm (17/25, 68%), Clark level IV/V (21/25, 84%), ulceration (16/25, 64%), and >3 mitoses/mm(2) (8/25, 32%). KIT gene mutations were detected in 11/25 cases (44%), and all these 11 cases displayed intratumor heterogeneity, that is, at least 2 tumor regions had different mutational profiles. The predicted effect of most mutations detected was detrimental to protein function. No significant correlations between histopathological variables and either KIT mutations or intratumor heterogeneity were observed. The hypothesis of intratumor heterogeneity of KIT gene mutations in acral lentiginous melanoma was supported. (AU)

• Processo FAPESP: 12/11513-6 - Avaliação de mutações no gene c-kit em melanoma acral-lentiginoso
• Beneficiário: Gilles Landman
• Modalidade de apoio: Auxílio à Pesquisa - Regular