Liquid biopsy has become widely applied in clinical medicine along with the progress in innovative technologies, such as next generation sequencing, but the origin of circulating tumor DNA (ctDNA) has not yet been precisely established. We reported bimodal peaks of long fragment circulating free DNA (cfDNA) of 5 kb and short fragment cfDNA of 170 bp in patients with advanced lung cancer, and both contained ctDNA. In this paper, we demonstrate that the total amount of cfDNA is higher when patients with lung cancer have extrathoracic metastases, and the amount of long fragment cfDNA is significantly higher in those patients. To investigate the origin of long fragment cfDNA, conditioned media isolated from lung cancer cell lines was fractionated. Long fragment cfDNA was found concomitant with extracellular vesicles (EVs), but short fragment cfDNA was not observed in any fractions. However, in peripheral blood from a metastatic animal model both fragments were detected even with those same lung cancer cell lines. In human plasma samples, long fragment cfDNA was observed in the same fraction as that from conditioned media, and short fragment cfDNA existed in the supernatant after centrifugation at 100,000g. Concentration of ctDNA in the supernatant was two times higher than that in plasma isolated by the conventional procedure. Long fragment cfDNA associated with tumor progression might therefore be released into peripheral blood, and it is possible that the long fragment cfDNA escapes degradation by co-existing with EVs. Examination of the biological characteristics of long fragment cfDNA is a logical subject of further investigation.
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PLoS One
January 2025
Department of Obstetrics and Gynaecology, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands.
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Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
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View Article and Find Full Text PDFSynth Biol (Oxf)
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Claret Bioscience LLC, 100 Enterprise Way, Suite A102, Scotts Valley, CA 95066, United States.
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View Article and Find Full Text PDFBest Pract Res Clin Obstet Gynaecol
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University of California, San Francisco, Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal-Fetal Medicine, 1825 Fourth St, Third Floor, San Francisco, CA, 94158, USA; University of California, San Francisco, Institute of Human Genetics, 1825 Fourth St, Third Floor, San Francisco, CA, 94158, USA. Electronic address:
Screening for fetal genetic disorders is a focus of prenatal care. Cell free DNA (cfDNA) screening for aneuploidies became available in 2011. Initially available only to high-risk individuals, this test is now standard of care in many settings.
View Article and Find Full Text PDFClin Chim Acta
December 2024
Faculty of Biotechnology, University of Surabaya, Surabaya 60292, Indonesia. Electronic address:
T2DM detection methods are commonly used in teens and adults but are generally unsuitable to unborn fetuses in the context of non-invasive prenatal testing (NIPT). Biophysical and biochemical tests for fetuses are often invasive, carry risks, and have low sensitivity and specificity, with no direct method available to diagnose T2DM in utero. In contrast, cell-free DNA (cfDNA) is known have high sensitivity (93-98 %) and specificity (94-100 %) for cancer detection and fetal genetic disorders (trisomy 21, 8, and 13) making it applicable for fetal epigenetic and genetic analysis, including T2DM early detection.
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