Long interspersed nucleotide element-1 hypomethylation in canine malignant mucosal melanoma
Long interspersed nucleotide element-1 hypomethylation in canine malignant mucosal melanoma
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DOI：
10.1111/vco.12591
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发表时间：
2020-03-28
影响因子：
2.1
通讯作者：
Kimura, Takashi
中科院分区：
文献类型：
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作者：
Ishizaki, Teita;Yamazaki, Jumpei;Kimura, Takashi
犬恶性黑色素瘤是一种常见的恶性肿瘤，病死率高，是临床上的重要疾病。DNA甲基化被认为是一种潜在的肿瘤发生机制，它通过启动子区的异常甲基化抑制基因转录。整体低甲基化也可以促进染色体不稳定性。目前关于犬恶性黑色素瘤中DNA甲基化的报道较少，因此，本研究的目的是检测长散布核苷酸元件-1（LINE-1）的DNA甲基化状态，作为该疾病全基因组甲基化变化的替代标记。我们通过亚硫酸氢盐焦磷酸测序法测定了41例犬黑色素瘤患者样本以及6个细胞系与正常粘膜相比的犬LINE-1序列启动子CpG岛（CGI）上两个相邻胞嘧啶-鸟嘌呤位点的DNA甲基化水平。存活率从主人或医疗记录中获得。我们发现正常粘膜中LINE-1基因的甲基化水平是甲基化的。有趣的是，黑色素瘤细胞系和临床黑色素瘤样品都显示出显著的低甲基化。此外，LINE-1甲基化水平较低的患者的预后比LINE-1甲基化水平较高的患者差，但差异未达到统计学显著性（P = 0.09）。在这里，我们证明LINE-1的低甲基化是一个表观遗传学异常的功能，在犬黑色素瘤与可能的预后价值。
Canine malignant melanoma is a common cancer with a high mortality rate and is a clinically important disease. DNA methylation has been considered to be a potential tumorigenic mechanism through aberrant DNA methylation at promoter region which represses gene transcription. Global hypomethylation could also facilitate chromosome instability. There are few reports regarding DNA methylation in canine malignant melanoma; therefore, the purpose of this study was to examine DNA methylation status of long interspersed nucleotide element-1 (LINE-1) to be a surrogate marker of genome-wide methylation changes in this disease. We measured levels of DNA methylation of two adjacent cytosine-guanine sites on CpG island (CGI) at the putative promoter of canine LINE-1 sequence by bisulphite-pyrosequencing in 41 canine melanoma patient samples as well as six cell lines compared with normal mucosae. The survival rates were obtained from owners or medical records. We found DNA methylation levels of LINE-1 in normal mucosae were methylated. Interestingly, both melanoma cell lines and clinical melanoma samples showed remarkable hypomethylation. In addition, patients with lower LINE-1 methylation showed worse prognosis than those with higher LINE-1 methylation, though the difference did not reach statistical significance (P = .09). Here, we demonstrate that hypomethylation of LINE-1 is an epigenetically aberrant feature in canine melanoma with possible prognostic value.