Acral Lentiginous Melanomas Harbour Intratumor Heterogeneity in BRAF Exon 15, With Mutations Distinct From V600E/V600K

Autor(es)

Fernandes, Mariana ^[1] ; Barcelos, Denise ^[1] ; Comodo, Andreia Neves ^[1] ; Guimaraes, Daiane Pereira ^[1] ; Lopes Carapeto, Fernando Cintra ^[1] ; Cardili, Leonardo ^[1] ; Moraes, Lais de Sousa ^[2] ; Cerutti, Janete ^[2] ; Landman, Gilles ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Pathol, Sao Paulo - Brazil

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

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF DERMATOPATHOLOGY; v. 41, n. 10, p. 733-740, OCT 2019.
• Citações Web of Science: 1

Resumo

The choice of appropriate therapeutic strategies may be influenced by intratumor heterogeneity and makes cancer treatment considerably more challenging. We aimed to evaluate the heterogeneity of BRAF exon 15 mutations in different areas of acral lentiginous melanoma (ALM). The entire exon 15 was sequenced in 4 different areas of paraffin-embedded samples from 26 patients with ALM. A total of 26 of 49 cases of >= 1 mm in depth of ALM identified by clinical, anatomical, and pathological data fulfilled the inclusion and exclusion criteria for this study. Tumors had a mean Breslow depth of 7.2 mm and an average mitotic index of 3 mitosis/ mm(2). Mutations distinct from the common V600E and V600K were detected in 31%, and intratumor heterogeneity was observed in 31% of samples. Interestingly, 63.5% of all mutations had been previously associated with cancer. Most (62.5%) of the missense BRAF exon 15 mutations found in the ALM samples examined here were deemed ``detrimental{''} for protein function according to at least 2 functional prediction programs, and 3 mutations (37.5%) were predicted to be ``neutral,{''} with no effect on protein function. BRAF exon 15 mutations were detected frequently in ALM and displayed heterogeneity, a finding to be further investigated. (AU)

• Processo FAPESP: 12/11408-8 - Avaliação dos genes BRAF (7q34), MAP2K1 (15q22.1-q22.33) e MAP2K2 (19p13.3) no melanoma acral lentiginoso
• Beneficiário: Gilles Landman
• Modalidade de apoio: Auxílio à Pesquisa - Regular