Angeles Arlou Kristina, Janke Florian, Bauer Simone, Christopoulos Petros, Riediger Anja Lisa, Sültmann Holger
Division of Cancer Genome Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany.
Cancers (Basel). 2021 Nov 10;13(22):5615. doi: 10.3390/cancers13225615.
Cell-free DNA (cfDNA) analysis using liquid biopsies is a non-invasive method to gain insights into the biology, therapy response, mechanisms of acquired resistance and therapy escape of various tumors. While it is well established that individual cancer treatment options can be adjusted by panel next-generation sequencing (NGS)-based evaluation of driver mutations in cfDNA, emerging research additionally explores the value of deep characterization of tumor cfDNA genomics and fragmentomics as well as nucleosome modifications (chromatin structure), and methylation patterns (epigenomics) for comprehensive and multi-modal assessment of cfDNA. These tools have the potential to improve disease monitoring, increase the sensitivity of minimal residual disease identification, and detection of cancers at earlier stages. Recent progress in emerging technologies of cfDNA analysis is summarized, the added potential clinical value is highlighted, strengths and limitations are identified and compared with conventional targeted NGS analysis, and current challenges and future directions are discussed.
使用液体活检进行游离DNA（cfDNA）分析是一种非侵入性方法，可深入了解各种肿瘤的生物学特性、治疗反应、获得性耐药机制和治疗逃逸情况。虽然基于二代测序（NGS）的cfDNA驱动突变评估能够调整个体癌症治疗方案这一点已得到充分证实，但新兴研究还进一步探索了对肿瘤cfDNA基因组学、片段组学以及核小体修饰（染色质结构）和甲基化模式（表观基因组学）进行深度表征，以对cfDNA进行全面和多模式评估的价值。这些工具具有改善疾病监测、提高微小残留病识别灵敏度以及在更早阶段检测癌症的潜力。本文总结了cfDNA分析新兴技术的最新进展，突出了其潜在的临床附加价值，确定了其优势和局限性，并与传统靶向NGS分析进行了比较，同时讨论了当前面临的挑战和未来发展方向。
