Statistical analysis of mutant allele frequency level of circulating cell-free DNA and blood cells in healthy individuals

• Published in: Scientific reports Vol. 7; no. 1; pp. 7526 - 7
• Main Authors: Xia, Ligang, Li, Zhoufang, Zhou, Bo, Tian, Geng, Zeng, Lidong, Dai, Hongyu, Li, Xiaohua, Liu, Chaoyu, Lu, Shixin, Xu, Feiyue, Tu, Xiaonian, Deng, Fang, Xie, Yuancai, Huang, Weiren, He, Jiankui
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-08-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 45/22; 45/23; 45/47; 45/77; 692/308/53/2421; 692/700/139/1512; Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Cancer; Case-Control Studies; Cell-Free Nucleic Acids - blood; Cell-Free Nucleic Acids - genetics; Circulating Tumor DNA - blood; Circulating Tumor DNA - genetics; Deoxyribonucleic acid; DNA; Early Detection of Cancer; Female; Gene Expression; Gene Frequency; High-Throughput Nucleotide Sequencing; Humanities and Social Sciences; Humans; Leukocytes; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Male; Middle Aged; multidisciplinary; Mutation; Neoplasms - blood; Neoplasms - diagnosis; Neoplasms - genetics; Neoplasms - pathology; Nuclear Proteins - blood; Nuclear Proteins - genetics; Population genetics; Science; Science (multidisciplinary); Sequence Analysis, DNA; Statistical analysis; Tumors
• ISSN: 2045-2322; 2045-2322
• 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.