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Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology
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 wom...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997656/ https://www.ncbi.nlm.nih.gov/pubmed/33752803 http://dx.doi.org/10.7554/eLife.64356 |
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author | Gai, Wanxia Zhou, Ze Agbor-Enoh, Sean Fan, Xiaodan Lian, Sheng Jiang, Peiyong Cheng, Suk Hang Wong, John Chan, Stephen L Jang, Moon Kyoo Yang, Yanqin Liang, Raymond HS Chan, Wai Kong Ma, Edmond SK Leung, Tak Y Chiu, Rossa WK Valantine, Hannah Chan, KC Allen Lo, YM Dennis |
author_facet | Gai, Wanxia Zhou, Ze Agbor-Enoh, Sean Fan, Xiaodan Lian, Sheng Jiang, Peiyong Cheng, Suk Hang Wong, John Chan, Stephen L Jang, Moon Kyoo Yang, Yanqin Liang, Raymond HS Chan, Wai Kong Ma, Edmond SK Leung, Tak Y Chiu, Rossa WK Valantine, Hannah Chan, KC Allen Lo, YM Dennis |
author_sort | Gai, Wanxia |
collection | PubMed |
description | 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 hr 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. |
format | Online Article Text |
id | pubmed-7997656 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-79976562021-03-31 Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology Gai, Wanxia Zhou, Ze Agbor-Enoh, Sean Fan, Xiaodan Lian, Sheng Jiang, Peiyong Cheng, Suk Hang Wong, John Chan, Stephen L Jang, Moon Kyoo Yang, Yanqin Liang, Raymond HS Chan, Wai Kong Ma, Edmond SK Leung, Tak Y Chiu, Rossa WK Valantine, Hannah Chan, KC Allen Lo, YM Dennis eLife Medicine 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 hr 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. eLife Sciences Publications, Ltd 2021-03-23 /pmc/articles/PMC7997656/ /pubmed/33752803 http://dx.doi.org/10.7554/eLife.64356 Text en http://creativecommons.org/publicdomain/zero/1.0/ http://creativecommons.org/publicdomain/zero/1.0/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 (http://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Medicine Gai, Wanxia Zhou, Ze Agbor-Enoh, Sean Fan, Xiaodan Lian, Sheng Jiang, Peiyong Cheng, Suk Hang Wong, John Chan, Stephen L Jang, Moon Kyoo Yang, Yanqin Liang, Raymond HS Chan, Wai Kong Ma, Edmond SK Leung, Tak Y Chiu, Rossa WK Valantine, Hannah Chan, KC Allen Lo, YM Dennis Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology |
title | Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology |
title_full | Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology |
title_fullStr | Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology |
title_full_unstemmed | Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology |
title_short | Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology |
title_sort | applications of genetic-epigenetic tissue mapping for plasma dna in prenatal testing, transplantation and oncology |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997656/ https://www.ncbi.nlm.nih.gov/pubmed/33752803 http://dx.doi.org/10.7554/eLife.64356 |
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