RT Journal Article
SR Electronic
T1 Baseline mutation profiling of 1134 samples of circulating cell-free DNA and blood cells from healthy individuals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 089813
DO 10.1101/089813
A1 Ligang Xia
A1 Zhoufang Li
A1 Bo Zhou
A1 Geng Tian
A1 Lidong Zeng
A1 Hongyu Dai
A1 Fang Deng
A1 Yuancai Xie
A1 Shixin Lu
A1 Xiaohua Li
A1 Chaoyu Liu
A1 Weiren Huang
A1 Jiankui He
YR 2016
UL http://biorxiv.org/content/early/2016/11/26/089813.abstract
AB The molecular alteration in circulating cell-free DNA (cfDNA) in plasma can reflect the status of the human body in a timely manner. Hence, cfDNA has emerged as important biomarkers in clinical diagnostics, particularly in cancer. However, somatic mutations are also commonly found in healthy individuals, which extensively interfere with the diagnostic results in cancer. This study was designed to examine the background somatic mutations in white blood cells (WBC) and cfDNA for healthy controls based on the sequencing data from 1134 samples, to understand the patterns and origin of mutations detected in cfDNA. We determined the mutation frequencies in both the WBC and cfDNA groups of the samples by a panel of 50 cancer-associated genes which covered 20K nucleotide regions using ultra-deep sequencing with average depth >40000 folds. Our results showed that most of mutations in cfDNA originated from WBC. We also observed that NPM1 gene was the most frequently mutant 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 tumor DNA, and shielded light on developing the early cancer diagnosis by cfDNA sequencing.