Volik Stanislav, Alcaide Miguel, Morin Ryan D, Collins Colin
Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Mol Cancer Res. 2016 Oct;14(10):898-908. doi: 10.1158/1541-7786.MCR-16-0044. Epub 2016 Jul 15.
Precision oncology is predicated upon the ability to detect specific actionable genomic alterations and to monitor their adaptive evolution during treatment to counter resistance. Because of spatial and temporal heterogeneity and comorbidities associated with obtaining tumor tissues, especially in the case of metastatic disease, traditional methods for tumor sampling are impractical for this application. Known to be present in the blood of cancer patients for decades, cell-free DNA (cfDNA) is beginning to inform on tumor genetics, tumor burden, and mechanisms of progression and drug resistance. This substrate is amenable for inexpensive noninvasive testing and thus presents a viable approach to serial sampling for screening and monitoring tumor progression. The fragmentation, low yield, and variable admixture of normal DNA present formidable technical challenges for realization of this potential. This review summarizes the history of cfDNA discovery, its biological properties, and explores emerging technologies for clinically relevant sequence-based analysis of cfDNA in cancer patients. Molecular barcoding (or Unique Molecular Identifier, UMI)-based methods currently appear to offer an optimal balance between sensitivity, flexibility, and cost and constitute a promising approach for clinically relevant assays for near real-time monitoring of treatment-induced mutational adaptations to guide evidence-based precision oncology. Mol Cancer Res; 14(10); 898-908. ©2016 AACR.
精准肿瘤学基于检测特定可操作基因组改变以及在治疗过程中监测其适应性进化以对抗耐药性的能力。由于与获取肿瘤组织相关的空间和时间异质性以及合并症，尤其是在转移性疾病的情况下，传统的肿瘤采样方法在这种应用中并不实用。游离DNA（cfDNA）几十年来一直被认为存在于癌症患者的血液中，它开始为肿瘤遗传学、肿瘤负荷以及进展和耐药机制提供信息。这种底物适合进行低成本的非侵入性检测，因此为连续采样以筛查和监测肿瘤进展提供了一种可行的方法。正常DNA的片段化、低产量和可变混合为实现这一潜力带来了巨大的技术挑战。本综述总结了cfDNA的发现历史、其生物学特性，并探索了用于对癌症患者cfDNA进行基于序列的临床相关分析的新兴技术。基于分子条形码（或独特分子标识符，UMI）的方法目前似乎在灵敏度、灵活性和成本之间提供了最佳平衡，并且构成了一种有前景的方法，用于进行临床相关检测以近乎实时地监测治疗诱导的突变适应性，从而指导基于证据的精准肿瘤学。《分子癌症研究》；14(10)；898 - 908。©2016美国癌症研究协会。
