![]() The circulation receives DNA from different tissues and organs within the body. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring, and cancer screening. 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. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumor-specific mutations. 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%. ![]() We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. 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. Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, China.Department of Pathology, Hong Kong Sanatorium & Hospital, China.Comprehensive Oncology Centre, Hong Kong Sanatorium & Hospital, China.Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, China.Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, China. ![]() Department of Statistics, The Chinese University of Hong Kong, China.Division of Intramural Research, National Heart, Lung and Blood Institute, United States.Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, United States.Genomic Research Alliance for Transplantation (GRAfT), United States.State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, China.Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, China.Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, China.
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