Identification of mutations in canine oral mucosal melanomas by exome sequencing and comparison with human melanomas

通过外显子组测序鉴定犬口腔粘膜黑色素瘤的突变并与人类黑色素瘤进行比较

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作者:Maria Lucia Zaidan Dagli, Márcia Kazumi Nagamine, Tatícia Lieh Ikeda, Ivone Izabel Mackowiak da Fonseca, Frederico Schmitt Kremer, Fabiana Kommling Seixas, Carolina Dagli Hernandez, João Vitor Pereira Leite, Cassia Correa Yasumaru, Cristina Oliveira Massoco, Ricardo Hsieh, Silvia Vanessa Lourenço, T

Abstract

Oral mucosal melanomas (OMMs) are aggressive neoplasms commonly found in dogs but rare in humans. Utilizing whole exome sequencing (WES), which focuses on protein-coding regions to reveal mutation profiles, we conducted a comparative analysis of canine OMM and human melanomas. This study involved DNA extraction, exome enrichment, and sequencing from three canine OMM cell lines (CMGD-2, CMGD-5, TLM-1), five canine OMM frozen samples, a human OMM cell line (MEMO), and a human commercial skin melanoma cell line (SK-MEL-28). The sequencing and subsequent analysis of FASTQ files yielded final variant files, leading to the identification of mutations. Our findings revealed a total of 500 mutated genes in canine OMM, including significant ones such as EP300, FAT4, JAK3, LRP1B, NCOR1, and NOTCH1. Notably, 82 shared mutations were identified between human melanomas and canine OMM genomes. These mutations were categorized based on the gene functions. The identification of these mutations provides critical insights that can pave the way for the development of novel therapeutic strategies for both canine and human OMM, offering hope for more effective treatments in the future.

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