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Methylation dependent gold adsorption behaviour identifies cancer derived extracellular vesicular DNA.
Nanoscale Horizons ( IF 9.7 ) Pub Date : 2020-06-04 , DOI: 10.1039/d0nh00258e
Abu Ali Ibn Sina 1 , Ting-Yun Lin , Ramanathan Vaidyanathan , Zhaoran Wang , Shuvashis Dey , Jing Wang , Andreas Behren , Alain Wuethrich , Laura G Carrascosa , Matt Trau
Affiliation  

Extracellular vesicles (EV) play a major role in intercellular communication by transmitting cellular materials (e.g. protein, RNA) among distant cells. Recent evidence suggests that they could also contribute to carrying DNA which could inform on the mutational status of the parent tumour DNA. Thus, the fundamental analysis of evDNA could open a better understanding of tumour metastasis and provide new pathways for noninvasive detection and monitoring of cancer. To explore the potential of evDNA for diagnostics, the isolation of pure evDNA from body fluids free of cfDNA contamination is crucial. Herein, we use a liposome based model system to develop an improved evDNA isolation protocol free from cfDNA contamination and evaluate the methylation dependent physicochemical properties of evDNA to develop a simple test for detecting cancer evDNA. Using a highly sensitive multiplex microelectrode device, we demonstrate that serum-evDNA derived from cancer patients show different solution and surface based properties than normal evDNA due to their different methylation landscape (i.e. methylscape). This microdevice allows simultaneous analysis of multiple samples in a single platform from as low as 500 pg μL−1 of evDNA.

中文翻译:

甲基化依赖的金吸附行为鉴定了癌症衍生的细胞外囊泡DNA。

细胞外囊泡(EV)通过传输细胞物质(例如,蛋白质,RNA)。最近的证据表明,它们也可能有助于携带DNA,从而可以告知亲本肿瘤DNA的突变状态。因此,对evDNA的基础分析可以更好地理解肿瘤转移,并为癌症的非侵入性检测和监测提供新的途径。为了探索evDNA的诊断潜力,从无cfDNA污染的体液中分离纯evDNA至关重要。本文中,我们使用基于脂质体的模型系统开发了一种无cfDNA污染的改进的evDNA分离方案,并评估了evDNA的甲基化依赖性理化特性,从而开发了一种检测癌症evDNA的简单测试。使用高度敏感的多重微电极装置,methylscape)。这种微型设备允许在单个平台上同时分析低至500 pgμL -1的evDNA的多个样品。
更新日期:2020-06-04
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