Plasma DNA End-Motif Profiling as a Fragmentomic Marker in Cancer, Pregnancy, and Transplantation
Top Cited Papers
- 1 May 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Discovery
- Vol. 10 (5), 664-673
- https://doi.org/10.1158/2159-8290.CD-19-0622
Abstract
Plasma DNA fragmentomics is an emerging area of research covering plasma DNA sizes, end points, and nucleosome footprints. In the present study, we found a significant increase in the diversity of plasma DNA end motifs in patients with hepatocellular carcinoma (HCC). Compared with patients without HCC. patients with HCC showed a preferential pattern of 4-mer end motifs. In particular, the abundance of plasma DNA motif CCCA was much lower in patients with HCC than in subjects without HCC. The aberrant end motifs were also observed in patients with other cancer types, including colorectal cancer, lung cancer, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma. We further observed that the profile of plasma DNA end motifs originating from the same organ. such as the liver, placenta, and hematopoietic cells. generally clustered together. The profile of end motifs may therefore serve as a class of biomarkers for liquid biopsy in oncology, noninvasive prenatal testing, and transplantation monitoring. SIGNIFICANCE: Plasma DNA molecules originating from the liver, HCC and other cancers, placenta, and hematopoietic cells each harbor a set of characteristic plasma DNA end motifs. Such markers carry tissue-of-origin information and represent a new class of biomarkers in the nascent field of fragmentomics.Funding Information
- Council of the Hong Kong SAR (T12-403/15-N, T12-401/16-W)
- Chinese University of Hong Kong (VCF2014021)
- Li Ka Shing Foundation
This publication has 24 references indexed in Scilit:
- Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulationBMC Genomics, 2015
- Noninvasive monitoring of infection and rejection after lung transplantationProceedings of the National Academy of Sciences of the United States of America, 2015
- Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessmentsProceedings of the National Academy of Sciences of the United States of America, 2015
- Lengthening and shortening of plasma DNA in hepatocellular carcinoma patientsProceedings of the National Academy of Sciences of the United States of America, 2015
- Detection of Circulating Tumor DNA in Early- and Late-Stage Human MalignanciesScience Translational Medicine, 2014
- Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencingProceedings of the National Academy of Sciences of the United States of America, 2013
- Nonhematopoietically Derived DNA Is Shorter than Hematopoietically Derived DNA in Plasma: A Transplantation ModelClinical Chemistry, 2012
- Maternal Plasma DNA Sequencing Reveals the Genome-Wide Genetic and Mutational Profile of the FetusScience Translational Medicine, 2010
- Differential expression analysis for sequence count dataGenome Biology, 2010
- Size Distributions of Maternal and Fetal DNA in Maternal PlasmaClinical Chemistry, 2004