Department of Gastrointestinal Surgery, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen, 518020, China.
Department of Biology, South University of Science and Technology of China, Shenzhen, 518055, China.
Sci Rep. 2017 Aug 8;7(1):7526. doi: 10.1038/s41598-017-06106-1.
Cell-free DNA (cfDNA) in plasma has emerged as a potential important biomarker in clinical diagnostics, particularly in cancer. However, somatic mutations are also commonly found in healthy individuals, which interfere with the effectiveness for cancer diagnostics. This study examined the background somatic mutations in white blood cells (WBC) and cfDNA in healthy controls based on sequencing data from 821 non-cancer individuals and several cancer samples with the aim of understanding the patterns of mutations detected in cfDNA. We determined the mutation allele frequencies in both WBC and cfDNA using a panel of 50 cancer-associated genes that covers 20 K-nucleotide region and ultra-deep sequencing with average depth >40000-fold. Our results showed that most of the mutations in cfDNA were highly correlated to WBC. We also observed that the NPM1 gene was the most frequently mutated gene in both WBC and cfDNA. Our study highlighted the importance of sequencing both cfDNA and WBC to improve the sensitivity and accuracy for calling cancer-related mutations from circulating tumour DNA, and shedded light on developing a strategy for early cancer diagnosis by cfDNA sequencing.
血浆中的无细胞 DNA（cfDNA）已成为临床诊断中一种有潜力的重要生物标志物，特别是在癌症方面。然而，体细胞突变在健康个体中也很常见，这会干扰癌症诊断的效果。本研究基于 821 名非癌症个体和一些癌症样本的测序数据，检查了健康对照个体白细胞（WBC）和 cfDNA 中的背景体细胞突变，旨在了解 cfDNA 中检测到的突变模式。我们使用涵盖 20 K 核苷酸区域的 50 个与癌症相关的基因panel 以及平均深度 >40000 倍的超深度测序，来确定 WBC 和 cfDNA 中的突变等位基因频率。我们的结果表明，cfDNA 中的大多数突变与 WBC 高度相关。我们还观察到，NPM1 基因是 WBC 和 cfDNA 中突变最频繁的基因。我们的研究强调了同时对 cfDNA 和 WBC 进行测序的重要性，以提高从循环肿瘤 DNA 中调用癌症相关突变的灵敏度和准确性，并为通过 cfDNA 测序进行早期癌症诊断制定了策略。
