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Extending Circulating Tumor DNA Analysis to Ultralow Abundance Mutations: Techniques and Challenges
ACS Sensors ( IF 8.9 ) Pub Date : 2018-02-14 00:00:00 , DOI: 10.1021/acssensors.7b00953
Andrew E. Rodda , Bradyn J. Parker , Andrew Spencer 1, 2 , Simon R. Corrie
Affiliation  

Liquid biopsies that analyze circulating tumor DNA (ctDNA) hold great promise in the guidance of clinical treatment for various cancers. However, the innate characteristics of ctDNA make it a difficult target: ctDNA is highly fragmented, and found at very low concentrations, both in absolute terms and relative to wildtype species. Clinically relevant target sequences often differ from the wildtype species by a single DNA base pair. These characteristics make analyzing mutant ctDNA a uniquely difficult process. Despite this, techniques have recently emerged for analyzing ctDNA, and have been used in pilot studies that showed promising results. These techniques each have various drawbacks, either in their analytical capabilities or in practical considerations, which restrict their application to many clinical situations. Many of the most promising potential applications of ctDNA require assay characteristics that are not currently available, and new techniques with these properties could have benefits in companion diagnostics, monitoring response to treatment and early detection. Here we review the current state of the art in ctDNA detection, with critical comparison of the analytical techniques themselves. We also examine the improvements required to expand ctDNA diagnostics to more advanced applications and discuss the most likely pathways for these improvements.

中文翻译:

将循环肿瘤DNA分析扩展至超低丰度突变:技术和挑战

分析循环肿瘤DNA(ctDNA)的液体活检在指导各种癌症的临床治疗方面具有广阔的前景。但是,ctDNA的先天特性使其成为一个困难的目标:ctDNA高度断裂,无论是绝对值还是相对于野生型物种,其浓度都非常低。临床上相关的靶序列通常与野生型物种的区别在于单个DNA碱基对。这些特性使得分析突变ctDNA成为一个独特的难题。尽管如此,最近出现了用于分析ctDNA的技术,并已用于显示出可喜结果的初步研究中。这些技术在分析能力或实际考虑方面均具有各种缺点,这限制了它们在许多临床情况下的应用。ctDNA的许多最有前途的潜在应用都需要当前尚不具备的测定特性,而具有这些特性的新技术可能会在伴随诊断,监测对治疗的反应和早期发现方面具有优势。在这里,我们对ctDNA检测的最新技术进行了回顾,并对分析技术本身进行了严格的比较。我们还将研究将ctDNA诊断扩展到更高级的应用程序所需的改进,并讨论实现这些改进的最可能途径。对分析技术本身进行严格的比较。我们还将研究将ctDNA诊断扩展到更高级的应用程序所需的改进,并讨论实现这些改进的最可能途径。与分析技术本身的严格比较。我们还将研究将ctDNA诊断扩展到更高级的应用程序所需的改进,并讨论实现这些改进的最可能途径。
更新日期:2018-02-14
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