PDF(Pubmed)
Abstract：
UNASSIGNED: Epigenetic alterations in uveal melanoma (UM) are still neither well characterized, nor understood. In this pilot study, we sought to provide a deeper insight into the possible role of epigenetic alterations in the pathogenesis of UM and their potential prognostic relevance. To this aim, we comprehensively profiled histone post-translational modifications (PTMs), which represent epigenetic features regulating chromatin accessibility and gene transcription, in UM formalin-fixed paraffin-embedded (FFPE) tissues, control tissues, UM cell lines, and healthy melanocytes.
UNASSIGNED: FFPE tissues of UM (n = 24), normal choroid (n = 4), human UM cell lines (n = 7), skin melanocytes (n = 6), and uveal melanocytes (n = 2) were analyzed through a quantitative liquid chromatography-mass spectrometry (LC-MS) approach.
UNASSIGNED: Hierarchical clustering showed a clear separation with several histone PTMs that changed significantly in a tumor compared to normal samples, in both tissues and cell lines. In addition, several acetylations and H4K20me1 showed lower levels in BAP1 mutant tumors. Some of these changes were also observed when we compared GNA11 mutant tumors with GNAQ tumors. The epigenetic profiling of cell lines revealed that the UM cell lines MP65 and UPMM1 have a histone PTM pattern closer to the primary tissues than the other cell lines analyzed.
UNASSIGNED: Our results suggest the existence of different histone PTM patterns that may be important for diagnosis and prognosis in UM. However, further analyses are needed to confirm these findings in a larger cohort. The epigenetic characterization of a panel of UM cell lines suggested which cellular models are more suitable for epigenetic investigations.
UNASSIGNED: FFPE tissues of UM (n = 24), normal choroid (n = 4), human UM cell lines (n = 7), skin melanocytes (n = 6), and uveal melanocytes (n = 2) were analyzed through a quantitative liquid chromatography-mass spectrometry (LC-MS) approach.
UNASSIGNED: Hierarchical clustering showed a clear separation with several histone PTMs that changed significantly in a tumor compared to normal samples, in both tissues and cell lines. In addition, several acetylations and H4K20me1 showed lower levels in BAP1 mutant tumors. Some of these changes were also observed when we compared GNA11 mutant tumors with GNAQ tumors. The epigenetic profiling of cell lines revealed that the UM cell lines MP65 and UPMM1 have a histone PTM pattern closer to the primary tissues than the other cell lines analyzed.
UNASSIGNED: Our results suggest the existence of different histone PTM patterns that may be important for diagnosis and prognosis in UM. However, further analyses are needed to confirm these findings in a larger cohort. The epigenetic characterization of a panel of UM cell lines suggested which cellular models are more suitable for epigenetic investigations.
摘要：
■葡萄膜黑色素瘤（UM）的表观遗传改变仍未得到很好的表征，也不理解。在这项试点研究中，我们试图更深入地了解表观遗传改变在UM发病机制中的可能作用及其潜在的预后相关性.为了这个目标,我们全面分析了组蛋白翻译后修饰(PTM)，代表调节染色质可及性和基因转录的表观遗传特征，在UM福尔马林固定石蜡包埋(FFPE)组织中，控制组织，UM细胞系，和健康的黑素细胞.
■UM的FFPE组织（n=24），正常脉络膜（n=4），人UM细胞系（n=7），皮肤黑素细胞（n=6），通过定量液相色谱-质谱（LC-MS）方法分析葡萄膜黑素细胞（n=2）。
■分层聚类显示，与正常样本相比，肿瘤中有几个组蛋白PTM明显变化，在组织和细胞系中。此外,几种乙酰化和H4K20me1在BAP1突变肿瘤中显示较低水平。当我们比较GNA11突变肿瘤与GNAQ肿瘤时,也观察到这些变化中的一些。细胞系的表观遗传谱分析表明，UM细胞系MP65和UPMM1的组蛋白PTM模式比其他分析的细胞系更接近原代组织。
■我们的结果表明存在不同的组蛋白PTM模式，这对于UM的诊断和预后可能很重要。然而,需要进一步分析以在更大的队列中证实这些发现.一组UM细胞系的表观遗传表征表明哪些细胞模型更适合于表观遗传研究。
■UM的FFPE组织（n=24），正常脉络膜（n=4），人UM细胞系（n=7），皮肤黑素细胞（n=6），通过定量液相色谱-质谱（LC-MS）方法分析葡萄膜黑素细胞（n=2）。
■分层聚类显示，与正常样本相比，肿瘤中有几个组蛋白PTM明显变化，在组织和细胞系中。此外,几种乙酰化和H4K20me1在BAP1突变肿瘤中显示较低水平。当我们比较GNA11突变肿瘤与GNAQ肿瘤时,也观察到这些变化中的一些。细胞系的表观遗传谱分析表明，UM细胞系MP65和UPMM1的组蛋白PTM模式比其他分析的细胞系更接近原代组织。
■我们的结果表明存在不同的组蛋白PTM模式，这对于UM的诊断和预后可能很重要。然而,需要进一步分析以在更大的队列中证实这些发现.一组UM细胞系的表观遗传表征表明哪些细胞模型更适合于表观遗传研究。
