Technical progress in circulating tumor DNA analysis using next generation sequencing
Technical progress in circulating tumor DNA analysis using next generation sequencing
复制标题
使用下一代测序进行循环肿瘤 DNA 分析的技术进展。
DOI：
10.1016/j.mcp.2019.101480
复制
发表时间：
2020-02-01
影响因子：
3.3
通讯作者：
Ge, Qinyu
中科院分区：
文献类型：
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作者：
Bai, Yunfei;Wang, Zexin;Ge, Qinyu
循环肿瘤DNA(CtDNA)是肿瘤来源的、碎片化的DNA，在体液中自由循环，主要在外周血中循环。最近，在癌症的检测和治疗中，ctDNA分析被认为是组织活检的补充。在ctDNA中可以检测到肿瘤细胞特有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中识别出可能导致治疗耐药的异种肿瘤突变，这将有助于癌症诊断、预后和实时监测，并为靶向治疗提供信息。然而，ctDNA仍然不是用于这一目的的常规方法，因为其检测技术缺乏足够的灵敏度，无法在科学研究和临床试验中可靠地使用。本文综述了基于下一代测序的ctDNA突变检测方法的最新进展，重点介绍了几种优化的文库制备方法，以提高ctDNA检测的敏感性和特异性。
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.