葡萄膜黑色素瘤（UM）是成人最常见的原发性眼内肿瘤，大约50%的患者会发生转移。表观遗传变化是癌症进展的主要因素。我们的目的是确定在 UM 细胞系中使用 DNA 甲基转移酶 (DNMT) 抑制剂是否可以改变甲基化谱。用氮胞苷处理四种原发性和转移性 UM 细胞系，并分析细胞增殖、集落形成和 BAP1 蛋白表达。比较了基因组和游离 (cf)DNA 甲基化。在所有细胞系中，氮胞苷处理对增殖、集落形成和放射敏感性产生剂量依赖性影响。甲基化分析揭示了根据 BAP1 表达的细胞系之间甲基化的差异。匹配的原代细胞系和转移细胞系显示出非常相似的模式。在已知对 UM 进展重要的通路（例如 PI3K/Akt 和 MAPK 信号传导）以及参与癌症进展的通路（例如干细胞潜能、细胞运动和侵袭的调节）中发现了变化。这些变化保留在基因组和游离 DNA 中。该数据表明 DNMT 抑制剂会导致 UM 细胞中 cfDNA 中保留的变化。结果表明，针对 UM 治疗中的甲基化并使用 cfDNA 甲基化监测治疗反应可能是一个有价值的工具。© 2024。作者。

Uveal melanoma (UM) is the most common primary intraocular tumour in adults, and approximately 50% of patients will develop metastasis. Epigenetic changes are a major factor in cancer progression. We aimed to determine whether methylation profiles could be altered using a DNA methyltransferase (DNMT) inhibitor in UM cell lines.Four primary and metastatic UM cell lines were treated with azacytidine and analysed for cell proliferation, colony formation, and BAP1 protein expression. Genomic and cell-free (cf)DNA methylation were compared.In all cell lines, azacytidine treatment resulted in dose-dependent effects on proliferation, colony formation, and radiosensitivity. Methylation profiling revealed differences in methylation between cell lines according to BAP1 expression. Matched primary and metastatic cell lines showed very similar patterns. Alterations were seen in pathways known to be important in UM progression, such as PI3K/Akt and MAPK signaling, and in pathways involved in cancer progression, such as regulation of stemlike potential, cell motility, and invasion. These changes were maintained in genomic and cell-free DNA.This data suggests that DNMT inhibitors cause changes in UM cells that are maintained in cfDNA. The results suggest that targeting methylation in UM treatment and monitoring response to treatment using cfDNA methylation could be a valuable tool.© 2024. The Author(s).