Oncology Biomarker Development, Roche (China) Holding Ltd, Pudong, Shanghai, China.
Oncology Biomarker Development, Genentech, Ltd, South San Francisco, USA.
Sci Rep. 2024 Feb 29;14(1):4973. doi: 10.1038/s41598-024-54361-w.
In China, circulating tumor DNA analysis is widely used and numerous assays are available. Systematic evaluation to help users make informed selections is needed. Nine circulating tumor DNA assays, including one benchmark assay, were evaluated using 23 contrived reference samples. There were two sample types (cell-free DNA and plasma samples), three circulating tumor DNA inputs (low, < 20 ng; medium, 20-50 ng; high, > 50 ng), two variant allele frequency ranges (low, 0.1-0.5%; intermediate, 0.5-2.5%), and four variant types (single nucleotide, insertion/deletion, structural, and copy number). Sensitivity, specificity, reproducibility, and all processes from cell-free DNA extraction to bioinformatics analysis were assessed. The test assays were generally comparable or superior to the benchmark assay, demonstrating high analytical sensitivity. Variations in circulating tumor DNA extraction and quantification efficiency, sensitivity, and reproducibility were observed, particularly at lower inputs. These findings will guide circulating tumor DNA assay choice for research and clinical studies, allowing consideration of multiple technical parameters.
在中国，循环肿瘤 DNA 分析得到了广泛应用，并且有许多检测方法可供选择。为了帮助用户做出明智的选择，需要进行系统的评估。本研究使用 23 个模拟参考样本，对 9 种循环肿瘤 DNA 检测方法（包括一种基准检测方法）进行了评估。这 9 种检测方法涉及两种样本类型（游离 DNA 和血浆样本）、三种循环肿瘤 DNA 输入量（低，<20ng；中，20-50ng；高，>50ng）、两个变异等位基因频率范围（低，0.1-0.5%；中，0.5-2.5%）和四种变异类型（单核苷酸、插入/缺失、结构和拷贝数）。评估了检测方法的灵敏度、特异性、重复性以及从游离 DNA 提取到生物信息学分析的所有过程。总体而言，检测方法与基准检测方法相当或优于基准检测方法，表现出较高的分析灵敏度。然而，在较低的输入量时，观察到循环肿瘤 DNA 提取和定量效率、灵敏度和重复性存在差异。这些发现将为研究和临床研究中的循环肿瘤 DNA 检测方法选择提供指导，使人们能够考虑多个技术参数。
