Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics.
Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics.
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DOI：
10.1038/s41551-021-00837-3
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发表时间：
2022-03
影响因子：
28.1
通讯作者：
中科院分区：
文献类型：
--
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癌症患者循环血浆中的游离 DNA (cfDNA) 含有肿瘤来源的 DNA 序列，可作为指导治疗、监测耐药性和早期检测癌症的生物标志物。然而，由于 cfDNA 浓度低，而且 cfDNA 片段化成短长度并且容易受到化学损伤，因此用于临床诊断应用的 cfDNA 分析仍然具有挑战性。独特分子标识符的条形码已被采用，以克服下一代测序的固有错误，这是高度多重 cfDNA 分析的主流方法。然而，许多方法学和分析前因素限制了基于 cfDNA 的液体活检癌症检测的临床灵敏度。在这篇综述中，我们描述了最先进的 cfDNA 分析技术，重点是多重分析策略，并讨论了突出的生物学和技术挑战，如果解决这些挑战，将大大改善癌症诊断和患者护理。
Cell-free DNA (cfDNA) in the circulating blood plasma of patients with cancer contains tumour-derived DNA sequences that can serve as biomarkers for guiding therapy, for the monitoring of drug resistance, and for the early detection of cancers. However, the analysis of cfDNA for clinical diagnostic applications remains challenging because of the low concentrations of cfDNA, and because cfDNA is fragmented into short lengths and is susceptible to chemical damage. Barcodes of unique molecular identifiers have been implemented to overcome the intrinsic errors of next-generation sequencing, which is the prevailing method for highly multiplexed cfDNA analysis. However, a number of methodological and pre-analytical factors limit the clinical sensitivity of the cfDNA-based detection of cancers from liquid biopsies. In this Review, we describe the state-of-the-art technologies for cfDNA analysis, with emphasis on multiplexing strategies, and discuss outstanding biological and technical challenges that, if addressed, would substantially improve cancer diagnostics and patient care.
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影响因子：
16.6
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通讯作者：
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