Circulating tumor DNA (ctDNA) is tumor-derived, fragmented DNA that circulates freely in body fluids, predominantly in the peripheral blood. Recently, ctDNA analysis has been suggested as a complement to tissue biopsy in the detection and treatment of cancer. Genetic and epigenetic information specific to tumor cells, including single nucleotide variations, copy number variations, and modified methylation patterns, can be detected in ctDNA. Importantly, mutations in heterogenous tumors that could impart therapeutic resistance could be identified in ctDNA, which would aid in cancer diagnosis, prognosis, and real-time monitoring, and inform treatment with targeted therapies. However, ctDNA is still not a routinely used method for this purpose, because its detection techniques lack adequate sensitivity for reliable use in scientific studies and clinical trials. This review provides an up-to-date summary of ctDNA mutation detection methods based on next generation sequencing, highlighting their advantages and limitations, and focusing in particular on several optimized library preparation methods for improved sensitivity and specificity of ctDNA detection.

中文翻译：

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使用下一代测序技术进行循环肿瘤DNA分析的技术进步。

循环肿瘤DNA（ctDNA）是肿瘤衍生的，片段化的DNA，可在体液中自由循环，主要在外周血中循环。最近，已建议将ctDNA分析作为组织活检的补充，以检测和治疗癌症。可以在ctDNA中检测到特定于肿瘤细胞的遗传和表观遗传信息，包括单核苷酸变异，拷贝数变异和修饰的甲基化模式。重要的是，可以在ctDNA中鉴定出可以赋予治疗抗性的异质性肿瘤突变，这将有助于癌症的诊断，预后和实时监测，并为靶向治疗提供信息。但是，ctDNA仍不是用于此目的的常规方法，因为其检测技术缺乏足够的灵敏度，无法可靠地用于科学研究和临床试验。这篇综述提供了基于下一代测序的ctDNA突变检测方法的最新摘要，着重介绍了它们的优点和局限性，并特别着重于几种优化的文库制备方法，以提高ctDNA检测的灵敏度和特异性。