Pesquisa de mutações no gene C-KIT em mastocitomas cutâneos e subcutâneos em cães, em Portugal
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2024
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Os mastocitomas são neoplasias malignas comuns no cão, representando cerca de 16% a 21% de todas as neoplasias cutâneas em cães. Alguns fatores de prognóstico importantes incluem, a classificação do grau histológico, metastização e marcadores de proliferação celular. Mutações no gene c-Kit têm sido descritas nos mastocitomas cutâneos (exões 8, 9 e 11) e subcutâneos (exão 11) tendo sido consideradas por alguns autores como indicadores negativos de prognóstico. Todavia, dada a variabilidade do comportamento biológico destes tumores, não existe, ainda, uma característica capaz de sinalizar todos os mastocitomas mais agressivos. Neste contexto, pretendeu-se, com o presente trabalho, avaliar a frequência de mutações nos exões 8, 9 e 11 do gene c-Kit em mastocitomas cutâneos e subcutâneos caninos e avaliar o seu potencial prognóstico, relacionando a sua presença com o tempo de sobrevida. Para tal, foram estudadas 59 amostras em bloco de parafina de mastocitomas caninos, cutâneos e subcutâneos, dos quais era conhecida informação sobre o desfecho clínico dois anos após o diagnóstico. Todas as amostras foram submetidas a extração de DNA e, posteriormente, a reação de PCR, para amplificação dos exões 8, 9 e 11 do gene c-Kit. A presença de mutações foi avaliada por eletroforese em gel de agarose (exão 11) ou por sequenciação dos produtos de PCR (exão 8 e 9). No total, foram observadas mutações em seis mastocitomas cutâneos (20,7%) e em um mastocitoma subcutâneo (3,3%). Foram identificadas mutações nos três exões em estudo. Nos animais que sobreviveram até dois anos após o diagnóstico, a frequência de mutações não sinónimas encontrada foi muito superior à observada nos cães que morreram devido ao tumor. A frequência de mutações não sinónimas em cães que morreram devido à neoplasia foi muito baixa. Apenas 14,3% dos animais com mutação morreram de causa relacionada com o tumor. Estes resultados levantam a questão da importância a ser atribuída às mutações no gene c-Kit como fator prognóstico e evidenciam a necessidade de mais estudos que possam contribuir para a clarificação deste assunto. Palavras-chave: mastocitomas, cães, prognóstico, mutações, gene c-Kit
Mast cell tumors are common canine malignant neoplasms, accounting for about 16% to 21% of all skin neoplasms in dogs. Some important prognostic factors include histological grade classification, metastasis and markers of cell proliferation. Mutations in the c-Kit gene have been described in cutaneous mast cell tumors (exons 8, 9 and 11) and subcutaneous mast cell tumors (exon 11) and have been considered by some authors as negative indicators of prognosis. However, given the variability of the biological behavior of these tumors, there is still no characteristic capable of signaling all the most aggressive mast cell tumors. In this context, the aim of the present study was to evaluate the frequency of mutations in exons 8, 9 and 11 of the c-Kit gene in canine cutaneous and subcutaneous mast cell tumors and to evaluate their prognostic potential, relating their presence to survival time. In order to accomplish this, 59 paraffin samples of canine, cutaneous and subcutaneous mast cell tumors, with known information about the clinical outcome two years after diagnosis, were studied. All samples were submitted to DNA extraction and PCR reaction for amplification of exons 8, 9 and 11 of the c-Kit gene. The presence of mutations was evaluated by agarose gel electrophoresis (exon 11) or by sequencing of PCR products (exon 8 and 9). Overall, mutations were observed in six cutaneous mast cell tumors (20,7%) and one subcutaneous mast cell tumor (3,3%). Mutations were identified in the three exons under study. In animals that survived up to two years after diagnosis, the frequency of non-synonymous mutations found was much higher than that observed in dogs that died because of the tumor. The frequency of non-synonymous mutations in dogs that died due to the neoplasm was very low. Only 14,3% of the animals with mutation died from tumor-related causes. These results raise the question of the importance to be attributed to mutations in the c-Kit gene as a prognostic factor and highlight the need for further studies that can contribute to the clarification of this subject. Key-words: mast cell tumors, dogs, prognosis, mutations, c-Kit gene
Mast cell tumors are common canine malignant neoplasms, accounting for about 16% to 21% of all skin neoplasms in dogs. Some important prognostic factors include histological grade classification, metastasis and markers of cell proliferation. Mutations in the c-Kit gene have been described in cutaneous mast cell tumors (exons 8, 9 and 11) and subcutaneous mast cell tumors (exon 11) and have been considered by some authors as negative indicators of prognosis. However, given the variability of the biological behavior of these tumors, there is still no characteristic capable of signaling all the most aggressive mast cell tumors. In this context, the aim of the present study was to evaluate the frequency of mutations in exons 8, 9 and 11 of the c-Kit gene in canine cutaneous and subcutaneous mast cell tumors and to evaluate their prognostic potential, relating their presence to survival time. In order to accomplish this, 59 paraffin samples of canine, cutaneous and subcutaneous mast cell tumors, with known information about the clinical outcome two years after diagnosis, were studied. All samples were submitted to DNA extraction and PCR reaction for amplification of exons 8, 9 and 11 of the c-Kit gene. The presence of mutations was evaluated by agarose gel electrophoresis (exon 11) or by sequencing of PCR products (exon 8 and 9). Overall, mutations were observed in six cutaneous mast cell tumors (20,7%) and one subcutaneous mast cell tumor (3,3%). Mutations were identified in the three exons under study. In animals that survived up to two years after diagnosis, the frequency of non-synonymous mutations found was much higher than that observed in dogs that died because of the tumor. The frequency of non-synonymous mutations in dogs that died due to the neoplasm was very low. Only 14,3% of the animals with mutation died from tumor-related causes. These results raise the question of the importance to be attributed to mutations in the c-Kit gene as a prognostic factor and highlight the need for further studies that can contribute to the clarification of this subject. Key-words: mast cell tumors, dogs, prognosis, mutations, c-Kit gene
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VETERINARY MEDICINE, DOGS, MAST CELL TUMOR, PROGNOSIS, MESTRADO INTEGRADO EM MEDICINA VETERINÁRIA, VETERINÁRIA, MEDICINA VETERINÁRIA, CÃES, MASTOCITOMAS, PROGNÓSTICOS, Mestrado Integrado em Medicina Veterinária