Characterization 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.
Characterization 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.
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DOI：
10.1002/1878-0261.13041
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发表时间：
2021-09
影响因子：
6.6
通讯作者：
Xing J
中科院分区：
文献类型：
--
作者：
Jin C;Liu X;Zheng W;Su L;Liu Y;Guo X;Gu X;Li H;Xu B;Wang G;Yu J;Zhang Q;Bao D;Wan S;Xu F;Lai X;Liu J;Xing J
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. Circulating cell‐free DNA (cfDNA) fragmentomics, encompassing the measurement of cfDNA length and short nucleotide motifs at cfDNA ends, is an emerging field in cancer diagnostics. In this study, we utilized whole‐genome sequencing data of cfDNA in patients with hepatocellular carcinoma (HCC). We observed that representative abnormal copy number variation (CNV) alterations and shorter fragment size (< 150 bp) selection enhanced the accuracy of CNV detection and improved the clinical utility of ctDNA in HCC. We also discovered a strong correlation of end motif type to fragment size and revealed similar fragment size characteristics of 4‐mer end motifs between patients with HCC and hepatitis B virus.
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影响因子：
--
作者：
Li, Bingshan;Zhan, Xiaowei;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
影响因子：
11.5
作者：
Kaseb, Ahmed O.;Sanchez, Nora S.;Sen, Shiraj;Kelley, Robin K.;Tan, Benjamin;Bocobo, Andrea G.;Lim, Kian H.;Abdel-Wahab, Reham;Uemura, Marc;Pestana, Roberto Carmagnani;Qiao, Wei;Xiao, Lianchun;Morris, Jeffrey;Amin, Hesham M.;Hassan, Manal M.;Rashid, Asif;Banks, Kimberly C.;Lanman, Richard B.;Talasaz, AmirAli;Mills-Shaw, Kenna R.;George, Bhawana;Haque, Abedul;Raghav, Kanwal P. S.;Wolff, Robert A.;Yao, James C.;Meric-Bernstam, Funda;Ikeda, Sadakatsu;Kurzrock, Razelle
通讯作者：
Kurzrock, Razelle
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
DOI：
10.1073/pnas.1500076112
发表时间：
2015-03-17
影响因子：
11.1
作者：
Jiang, Peiyong;Chan, Carol W. M.;Lo, Y. M. Dennis
通讯作者：
Lo, Y. M. Dennis
影响因子：
4.4
作者：
Fernandez-Banet, Julio;Lee, Nikki P.;Kan, Zhengyan
通讯作者：
Kan, Zhengyan