Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
Elife. 2021 Mar 23;10:e64356. doi: 10.7554/eLife.64356.
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.
我们开发了遗传-表观遗传组织图谱（GETMap）技术，通过比较携带非基因组遗传变异的血浆 DNA 的甲基化谱，来确定这些变异在血浆中的组织来源。我们通过证明在孕妇中，携带胎儿特异性等位基因的循环 DNA 完全来自胎盘，验证了这种方法的有效性。在肺移植受者中，我们发现，在移植后 72 小时，携带供体特异性等位基因的血浆 DNA 中只有 17%来自肺部，而造血细胞占 78%。在肝细胞癌患者中，肝脏被确定为携带肿瘤特异性突变的血浆 DNA 的主要来源。在一名患有淋巴瘤的孕妇中，携带癌症突变和胎儿特异性等位基因的血浆 DNA 分子分别被准确地显示来自淋巴细胞和胎盘。分析携带遗传变异的血浆 DNA 的组织来源，对于非侵入性产前检测、移植监测和癌症筛查具有潜在的应用价值。
