Open AccessCharacterization of fragment sizes, copy number aberrations and 4‐mer end motifs in cell‐free DNA of hepatocellular carcinoma for enhanced liquid biopsy‐based cancer detection
Author(s) -
Jin Chao,
Liu Xiaonan,
Zheng Wenyuan,
Su Liping,
Liu Yang,
Guo Xu,
Gu Xiaoming,
Li Hongping,
Xu Bo,
Wang Gang,
Yu Jiyan,
Zhang Qiong,
Bao Dengke,
Wan Shaogui,
Xu Fei,
Lai Xiaohuan,
Liu Jiayun,
Xing Jinliang
Publication year - 2021
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.13041
Subject(s) - hepatocellular carcinoma , copy number variation , biology , hepatitis b virus , deep sequencing , dna , microbiology and biotechnology , cancer research , genome , gene , virology , genetics , virus
Circulating cell‐free DNA (cfDNA) fragmentomics, which encompasses the measurement of cfDNA length and short nucleotide motifs at the ends of cfDNA molecules, is an emerging field for cancer diagnosis. The utilization of cfDNA fragmentomics for the diagnosis of patients with hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) is currently limited. In this study, we utilized whole‐genome sequencing data of cfDNA in samples from patients with HCC ( n = 197) and HBV ( n = 187) to analyze the association of fragment size selection (< 150 bp) with tumor fraction (TF), copy number variation (CNV) alterations and the change in the proportion of 4‐mer end motifs in HCC and HBV samples. Our analyses identified five typical CNV markers (i.e. loss in chr1p, chr4q and chr8p, and gain in chr1q and chr8q) in cfDNA with a cumulatively positive rate of ˜ 95% in HCC samples. Size selection (< 150 bp) significantly enhanced TF and CNV signals in HCC samples. Additionally, three 4‐mer end motifs (CCCA, CCTG and CCAG) were identified as preferred end motifs in HCC samples. We identified 139 end motifs significantly associated with fragment size that showed similar patterns of associations between patients with HCC and HBV, suggesting that end motifs might be inherently coupled with fragment size by a ubiquitous mechanism. Here we conclude that CNV markers, fragment size selection and end‐motif pattern in cfDNA have potential for effective detection of patients with HCC.