Avaliação da heterogeneidade intratumoral de mutações no gene kit em melanoma acral-lentiginoso

• Ano de defesa: 2014
• Autor(a) principal: Navarro, Andreia Neves Comodo [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Heterogeneidade; Intratumoral; Mutações; Gene kit; Melanoma acral lentiginoso
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=1339614; http://repositorio.unifesp.br/handle/11600/48550

Introduction: Melanoma is a malignant transformation of melanocytes. Acral lentiginous melanoma subtype occur more often in Afro-descendants and Asian population and have a more aggressive biologic nature than other subtypes. Acral lentiginous melanoma are found in the palms, soles, and nails. Genetic characteristics of these tumors seem to determine the therapeutic efficacy. KIT gene encodes a tyrosine-kinase receptor whose ligand is the stem cell factor, a growth factor that plays a key role in melanocyte formation. KIT mutations permanently activates the gene without any binding to the ligand and has been identified in gastrointestinal stromal tumors, in certain leukemias, in mastocytoses and seminomas, as well as melanomas. The aim of this study is to evaluate the presence and heterogeneity of KIT mutations in primary acral lentiginous melanoma by analysis of different areas of the same tumors. Methods: 25 formalin-fixed paraffin-embedded samples from acral lentiginous melanoma were obtained from the archives of the Department of Pathology, Escola Paulista de Medicina, Universidade Federal de São Paulo. Four different areas of each tumor were manually microdissected for DNA extraction. We evaluated the mutations by exons 11 and 13 sequencing. Results: Mean age was 63 years-old and there was a female predominance (52%). According to histological criteria patients had advanced melanomas: Breslow>4mm in 68%, Clark VI/V in 84% and ulceration in 64%. KIT mutations were found in 11/25 specimens (44%). Mutated specimens were all heterogeneous. Protein function impairment was predicted in the majority of mutations described herein. There is no significant correlation between histological criteria and tumor mutation. Conclusion: Acral-Lentiginous Melanomas have intratumoral KIT mutation heterogeneity.