Bronkhorst Abel Jacobus, Wentzel Johannes F, Aucamp Janine, van Dyk Etresia, du Plessis Lissinda H, Pretorius Piet J
Centre for Human Metabolomics, Biochemistry Division, North-West University, Potchefstroom, 2520, South Africa.
Centre of Excellence for Pharmaceutical Sciences (PHARMACEN), North-West University, Potchefstroom, 2520, South Africa.
Adv Exp Med Biol. 2016;924:19-24. doi: 10.1007/978-3-319-42044-8_4.
Non-invasive screening that utilizes cell-free DNA (cfDNA) offers remarkable potential as a method for the early detection of genetic disorders and a wide variety of cancers. Unfortunately, one of the most prominent elements delaying the translation of cfDNA analyses to clinical practice is the lack of knowledge regarding its origin and composition. The elucidation of the origin of cfDNA is complicated by the apparently arbitrary variability of quantitative and qualitative characteristics of cfDNA in the blood of healthy as well as diseased individuals. These factors may contribute to false positive/negative results when applied to clinical pathology. Although many have acknowledged that this is a major problem, few have addressed it. We believe that many of the current difficulties encountered in in vivo cfDNA studies can be partially circumvented by in vitro models. The results obtained in this study indicate that the release of cfDNA from 143B cells is not a consequence of apoptosis, necrosis or a product of DNA replication, but primarily the result of actively released DNA, perhaps in association with a protein complex. Moreover, this study demonstrates the potential of in vitro cell culture models to obtain useful information about the phenomenon of cfDNA.
利用游离DNA(cfDNA)进行的非侵入性筛查作为一种早期检测遗传疾病和多种癌症的方法具有巨大潜力。不幸的是,阻碍cfDNA分析转化为临床实践的最突出因素之一是缺乏对其来源和组成的了解。健康个体和患病个体血液中cfDNA的定量和定性特征存在明显的任意变异性,这使得阐明cfDNA的来源变得复杂。这些因素应用于临床病理学时可能导致假阳性/阴性结果。尽管许多人都承认这是一个主要问题,但很少有人解决它。我们认为,目前在体内cfDNA研究中遇到的许多困难可以通过体外模型部分规避。本研究获得的结果表明,143B细胞释放cfDNA不是凋亡、坏死的结果,也不是DNA复制的产物,而是主要是主动释放DNA的结果,可能与一种蛋白质复合物有关。此外,本研究证明了体外细胞培养模型在获取有关cfDNA现象的有用信息方面的潜力。