Genetic-epigenetic tissue mapping for plasma DNA: applications in prenatal testing, transplantation and oncology
- The Chinese University of Hong Kong, Hong Kong
- Johns Hopkins School of Medicine, United States
- National Heart, Lung and Blood Institute, United States
- Hong Kong Sanatorium and Hospital, Hong Kong
Abstract
We developed Genetic-Epigenetic Tissue Mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung-transplant recipients, we showed that, at 72 hours after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles and hematopoietic cells contributed a median of 78%. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumor-specific mutations. In a pregnant woman with lymphoma, plasma DNA molecules carrying cancer mutations and fetal-specific alleles were accurately shown to be derived from the lymphocytes and placenta, respectively. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring and cancer screening.
Data availability
Sequencing data have been deposited in EGA under the accession code EGAS00001004788.
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Methylation analysis for plasma DNA of patients with organ transplantationThe European Genome-phenome Archive, EGAS00001004788.
Article and author information
Author details
Funding
Research Grants Council, University Grants Committee (Theme-based research scheme T12-403/15-N)
- Rossa W K Chiu
- K C Allen Chan
- Y M Dennis Lo
Research Grants Council, University Grants Committee (Theme-based research scheme T12-401/16-W)
- Rossa W K Chiu
- K C Allen Chan
- Y M Dennis Lo
Chinese University of Hong Kong (VCF2014021)
- Rossa W K Chiu
- K C Allen Chan
- Y M Dennis Lo
Grail (Collaborative research agreement)
- Rossa W K Chiu
- K C Allen Chan
- Y M Dennis Lo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Tony Yuen
Ethics
Human subjects: The project was approved by the Joint Chinese University of Hong Kong-Hospital Authority New Territories East Cluster Clinical Research Ethics Committee (approval reference number 2011.204). All participants provided written informed consent.
Version history
- Received: October 26, 2020
- Accepted: March 10, 2021
- Accepted Manuscript published: March 23, 2021 (version 1)
- Version of Record published: March 26, 2021 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Genetic-epigenetic tissue mapping for plasma DNA: applications in prenatal testing, transplantation and oncology
eLife 10:e64356.
https://doi.org/10.7554/eLife.64356
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