Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease

By J. Moss, J. Magenheim, D. Neiman, Hai Zemmour, Netanel Loyfer, A. Korach, Yaacov Samet, M. Maoz, H. Druid, P. Arner and 13 more. Nature Communications, 2018

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Methylation patterns of circulating cell-free DNA (cfDNA) contain rich information about recent cell death events in the body. Here, we present an approach for unbiased determination of the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types. The method is validated using in silico simulations as well as in vitro mixes of DNA from different tissue sources at known proportions. We show that plasma cfDNA of healthy donors originates from white blood cells (55%), erythrocyte progenitors (30%), vascular endothelial cells (10%) and hepatocytes (1%). Deconvolution of cfDNA from patients reveals tissue contributions that agree with clinical findings in sepsis, islet transplantation, cancer of the colon, lung, breast and prostate, and cancer of unknown primary. We propose a procedure which can be easily adapted to study the cellular contributors to cfDNA in many settings, opening a broad window into healthy and pathologic human tissue dynamics. The methylation status of circulating cell-free DNA (cfDNA) can be informative about recent cell death events. Here the authors present an approach to determine the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types, and find that cfDNA from patients reveals tissue contributions that agree with clinical findings.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/ee209e99bf50bedb2a5d7533197c5eb7e9ca2931

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Citations in the corpus

• ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. (2022, background): “In healthy people, plasma DNA arises primarily from cells of the haematopoietic lineage, 3-6 with concentrations ranging from negligible amounts to up to 100 ng of plasma DNA/ml of plasma.”