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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chan, Stephen L. Cheng, Suk Hang Ng, Simon S. M. Chan, Rebecca W. Y. Chiu, Rossa W. K. Wong, Raymond S. M. Leung, Tse Ngong Sun, Kun Wong, John Lo, Yuk Ming Dennis Tong, Yu K. Leung, Tak Y. Chan, Wai-kong Lai, Paul B. S. Ma, Edmond S. K. Jiang, Peiyong Cheng, Yvonne K. Y. Chan, K. C. Allen Liang, Raymond H. S. Hui, David S. C. |
| Description | Author Affiliation: Sun K ( Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China); Jiang P ( Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China); Chan KC ( Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China); Wong J ( Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China); Cheng YK ( Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China); Liang RH ( Comprehensive Oncology Centre, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China); Chan WK ( Department of Pathology, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China); Ma ES ( Department of Pathology, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China); Chan SL ( Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China); Cheng SH ( Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China); Chan RW ( Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China); Tong YK ( Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China); Ng SS ( Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China); Wong RS ( Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China); Hui DS ( Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China); Leung TN ( Obstetrics and Gynaecology Centre, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China.); Leung TY ( Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China); Lai PB ( State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China); Chiu RW ( Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China); Lo YM ( Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China); |
| Abstract | Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA and deconvolution of the sequencing data with reference to methylation profiles of different tissues, we developed a general approach for studying the major tissue contributors to the circulating DNA pool. We tested this method in pregnant women, patients with hepatocellular carcinoma, and subjects following bone marrow and liver transplantation. In most subjects, white blood cells were the predominant contributors to the circulating DNA pool. The placental contributions in the plasma of pregnant women correlated with the proportional contributions as revealed by fetal-specific genetic markers. The graft-derived contributions to the plasma in the transplant recipients correlated with those determined using donor-specific genetic markers. Patients with hepatocellular carcinoma showed elevated plasma DNA contributions from the liver, which correlated with measurements made using tumor-associated copy number aberrations. In hepatocellular carcinoma patients and in pregnant women exhibiting copy number aberrations in plasma, comparison of methylation deconvolution results using genomic regions with different copy number status pinpointed the tissue type responsible for the aberrations. In a pregnant woman diagnosed as having follicular lymphoma during pregnancy, methylation deconvolution indicated a grossly elevated contribution from B cells into the plasma DNA pool and localized B cells as the origin of the copy number aberrations observed in plasma. This method may serve as a powerful tool for assessing a wide range of physiological and pathological conditions based on the identification of perturbed proportional contributions of different tissues into plasma. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 40 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Carcinoma, Hepatocellular Genetics DNA Methylation DNA Liver Neoplasms Sequence Analysis, DNA Tissue Transplantation Algorithms B-Lymphocytes Metabolism Bone Marrow Transplantation Blood Chemistry DNA Copy Number Variations Fetus Liver Pathology Liver Transplantation Neutrophils Placenta Pregnancy T-Lymphocytes Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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