Comparison of sequencing assays for sensitive detection of circulating tumour DNA in stage IA-IV breast cancer

This study compared different assays for the detection of circulating tumour DNA (ctDNA) in serial plasma from stage IA-IV breast cancer patients, targeting structural variants (SVs), single nucleotide variants (SNVs) and/or somatic copy-number aberrations (SCNAs). SV-multiplex PCR, SNV-/SV-hybrid capture, and different depths of whole-genome sequencing (WGS) were used to evaluate ctDNA levels, demonstrating concordant results. SNV-hybrid capture targeting 1,347-7,491 mutations was the most sensitive assay, detecting 67% (36/54) of samples down to an allele fraction (AF) of 0.00024%. SV-multiplex PCR, targeting 21-47 mutations, detected 63% (34/54) of samples down to 0.00047% AF and has potential as a clinical assay.

本研究对比分析了针对 IA-IV 期乳腺癌患者连续血浆中循环肿瘤DNA（ctDNA）检测的不同检测方法，旨在检测结构变异（SVs）、单核苷酸变异（SNVs）以及体细胞拷贝数异常（SCNAs）。研究采用了 SV-多重PCR、SNV-/SV-杂交捕获以及不同深度全基因组测序（WGS）等方法来评估 ctDNA 水平，结果显示出高度一致性。针对 1,347-7,491 个突变点的 SNV-杂交捕获检测方法灵敏度最高，能够检测到 67%（36/54）的样本，直至等位基因频率（AF）降至 0.00024%。针对 21-47 个突变点的 SV-多重PCR 检测方法能够检测到 63%（34/54）的样本，直至 AF 降至 0.00047%，并具有作为临床检测方法的潜力。