Cell-free DNA donor fraction analysis in pediatric and adult heart transplant patients by multiplexed allele-specific quantitative PCR: Validation of a rapid and highly sensitive clinical test for stratification of rejection probability


Autoři: Paula E. North aff001;  Emily Ziegler aff003;  Donna K. Mahnke aff003;  Karl D. Stamm aff003;  Angela Thomm aff003;  Paul Daft aff003;  Mary Goetsch aff004;  Huan ling Liang aff004;  Maria Angeles Baker aff003;  Adam Vepraskas aff003;  Chris Rosenau aff003;  Mahua Dasgupta aff005;  Pippa Simpson aff005;  Michael E. Mitchell aff002;  Aoy Tomita-Mitchell aff004
Působiště autorů: Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America aff001;  Childrens Hospital of Wisconsin, Milwaukee, Wisconsin, United States of America aff002;  TAI Diagnostics, Inc., Wauwatosa, Wisconsin, United States of America aff003;  Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America aff004;  Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227385

Souhrn

Lifelong noninvasive rejection monitoring in heart transplant patients is a critical clinical need historically poorly met in adults and unavailable for children and infants. Cell-free DNA (cfDNA) donor-specific fraction (DF), a direct marker of selective donor organ injury, is a promising analytical target. Methodological differences in sample processing and DF determination profoundly affect quality and sensitivity of cfDNA analyses, requiring specialized optimization for low cfDNA levels typical of transplant patients. Using next-generation sequencing, we previously correlated elevated DF with acute cellular and antibody-mediated rejection (ACR and AMR) in pediatric and adult heart transplant patients. However, next-generation sequencing is limited by cost, TAT, and sensitivity, leading us to clinically validate a rapid, highly sensitive, quantitative genotyping test, myTAIHEART®, addressing these limitations. To assure pre-analytical quality and consider interrelated cfDNA measures, plasma preparation was optimized and total cfDNA (TCF) concentration, DNA fragmentation, and DF quantification were validated in parallel for integration into myTAIHEART reporting. Analytical validations employed individual and reconstructed mixtures of human blood-derived genomic DNA (gDNA), cfDNA, and gDNA sheared to apoptotic length. Precision, linearity, and limits of blank/detection/quantification were established for TCF concentration, DNA fragmentation ratio, and DF determinations. For DF, multiplexed high-fidelity amplification followed by quantitative genotyping of 94 SNP targets was applied to 1168 samples to evaluate donor options in staged simulations, demonstrating DF call equivalency with/without donor genotype. Clinical validation studies using 158 matched endomyocardial biopsy-plasma pairs from 76 pediatric and adult heart transplant recipients selected a DF cutoff (0.32%) producing 100% NPV for ≥2R ACR. This supports the assay’s conservative intended use of stratifying low versus increased probability of ≥2R ACR. myTAIHEART is clinically validated for heart transplant recipients ≥2 months old and ≥8 days post-transplant, expanding opportunity for noninvasive transplant rejection assessment to infants and children and to all recipients >1 week post-transplant.

Klíčová slova:

Biopsy – Blood – Blood plasma – Cardiac transplantation – DNA fragmentation – Genotyping – White blood cells – Alu elements


Zdroje

1. Hammer S, Meisner F, Dirschedl P, Fraunberger P, Meiser B, Reichart B, et al. Procalcitonin for differential diagnosis of graft rejection and infection in patients with heart and/or lung grafts. Intensive care medicine. 2000;26 Suppl 2:S182–6

2. Mena C, Wencker D, Krumholz HM, McNamara RL. Detection of heart transplant rejection in adults by echocardiographic diastolic indices: a systematic review of the literature. Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography. 2006;19(10):1295–300

3. Vermes E, Pantaleon C, Auvet A, Cazeneuve N, Machet MC, Delhommais A, et al. Cardiovascular magnetic resonance in heart transplant patients: diagnostic value of quantitative tissue markers: T2 mapping and extracellular volume fraction, for acute rejection diagnosis. Journal of cardiovascular magnetic resonance: official journal of the Society for Cardiovascular Magnetic Resonance. 2018;20(1):59.

4. Patel PC, Hill DA, Ayers CR, Lavingia B, Kaiser P, Dyer AK, et al. High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant. Circulation Heart failure. 2014;7(3):463–9 doi: 10.1161/CIRCHEARTFAILURE.113.000697 24733367

5. Sinha AM, Breithardt OA, Schmid M, Stellbrink C. Brain natriuretic peptide release in cardiac surgery patients. The Thoracic and cardiovascular surgeon. 2005;53(3):138–43 doi: 10.1055/s-2005-837453 15926091

6. Talha S, Charloux A, Enache I, Piquard F, Geny B. Mechanisms involved in increased plasma brain natriuretic peptide after heart transplantation. Cardiovascular research. 2011;89(2):273–81 doi: 10.1093/cvr/cvq331 20962105

7. Sparks JD, Boston U, Eghtesady P, Canter CE. B-type natriuretic peptide trends after pediatric heart transplantation. Pediatric transplantation. 2014;18(5):477–84 doi: 10.1111/petr.12288 24922348

8. Behr TM, Feucht HE, Richter K, Reiter C, Spes CH, Pongratz D, et al. Detection of humoral rejection in human cardiac allografts by assessing the capillary deposition of complement fragment C4d in endomyocardial biopsies. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 1999;18(9):904–12

9. Husain AN, Mirza KM, Fedson SE. Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 2017;36(12):1329–35

10. Luk A, Alba AC, Butany J, Tinckam K, Delgado D, Ross HJ. C4d immunostaining is an independent predictor of cardiac allograft vasculopathy and death in heart transplant recipients. Transplant international: official journal of the European Society for Organ Transplantation. 2015;28(7):857–63

11. Berry GJ, Burke MM, Andersen C, Bruneval P, Fedrigo M, Fishbein MC, et al. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 2013;32(12):1147–6210. https://doi.org/10.1016/j.healun.2013.08.011

12. Nakhleh RE, Jones J, Goswitz JJ, Anderson EA, Titus J. Correlation of endomyocardial biopsy findings with autopsy findings in human cardiac allografts. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 1992;11(3 Pt 1):479–85

13. Yong E. Cancer biomarkers: Written in blood. Nature. 2014;511(7511):524–6 doi: 10.1038/511524a 25079538

14. Shah Z, Vuddanda V, Rali AS, Pamulapati H, Masoomi R, Gupta K. National Trends and Procedural Complications from Endomyocardial Biopsy: Results from the National Inpatient Sample, 2007–2014. Cardiology. 2018;141(3):125–31 doi: 10.1159/000493786 30517933

15. Yilmaz A, Kindermann I, Kindermann M, Mahfoud F, Ukena C, Athanasiadis A, et al. Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance. Circulation. 2010;122(9):900–9 doi: 10.1161/CIRCULATIONAHA.109.924167 20713901

16. Saraiva F, Matos V, Goncalves L, Antunes M, Providencia LA. Complications of endomyocardial biopsy in heart transplant patients: a retrospective study of 2117 consecutive procedures. Transplantation proceedings. 2011;43(5):1908–12 doi: 10.1016/j.transproceed.2011.03.010 21693299

17. Fiorelli AI, Coelho GH, Oliveira JL Jr., Aiello VD, Benvenuti LA, Santos A, et al. Endomyocardial biopsy as risk factor in the development of tricuspid insufficiency after heart transplantation. Transplantation proceedings. 2009;41(3):935–7 doi: 10.1016/j.transproceed.2009.02.011 19376392

18. Baraldi-Junkins C, Levin HR, Kasper EK, Rayburn BK, Herskowitz A, Baughman KL. Complications of endomyocardial biopsy in heart transplant patients. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 1993;12(1 Pt 1):63–7

19. Pophal SG, Sigfusson G, Booth KL, Bacanu SA, Webber SA, Ettedgui JA, et al. Complications of endomyocardial biopsy in children. Journal of the American College of Cardiology. 1999;34(7):2105–10 doi: 10.1016/s0735-1097(99)00452-0 10588231

20. Winters GL. The challenge of endomyocardial biopsy interpretation in assessing cardiac allograft rejection. Current opinion in cardiology. 1997;12(2):146–52 doi: 10.1097/00001573-199703000-00009 9192483

21. Winters GL. The challenge of endomyocardial biopsy interpretation in assessing cardiac allograft rejection. Current opinion in cardiology. 1997;12(2):146–52 doi: 10.1097/00001573-199703000-00009 9192483

22. Yang HM, Lai CK, Gjertson DW, Baruch-Oren T, Ra SH, Watts W, et al. Has the 2004 revision of the International Society of Heart and Lung Transplantation grading system improved the reproducibility of the diagnosis and grading of cardiac transplant rejection? Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology. 2009;18(4):198–204

23. Crespo-Leiro MG, Zuckermann A, Bara C, Mohacsi P, Schulz U, Boyle A, et al. Concordance among pathologists in the second Cardiac Allograft Rejection Gene Expression Observational Study (CARGO II). Transplantation. 2012;94(11):1172–7 doi: 10.1097/TP.0b013e31826e19e2 23222738

24. Peyster EG, Madabhushi A, Margulies KB. Advanced Morphologic Analysis for Diagnosing Allograft Rejection: The Case of Cardiac Transplant Rejection. Transplantation. 2018;102(8):1230–9. doi: 10.1097/TP.0000000000002189 29570167

25. Subherwal S, Kobashigawa JA, Cogert G, Patel J, Espejo M, Oeser B. Incidence of acute cellular rejection and non-cellular rejection in cardiac transplantation. Transplantation proceedings. 2004;36(10):3171–2 doi: 10.1016/j.transproceed.2004.10.048 15686721

26. Angelini A, Andersen CB, Bartoloni G, Black F, Bishop P, Doran H, et al. A web-based pilot study of inter-pathologist reproducibility using the ISHLT 2004 working formulation for biopsy diagnosis of cardiac allograft rejection: the European experience. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 2011;30(11):1214–20

27. Wagner SJ, Turek JW, Maldonado J, Staron M, Edens RE. Less Is More in Post Pediatric Heart Transplant Care. The Annals of thoracic surgery. 2019;107(1):165–71 doi: 10.1016/j.athoracsur.2018.06.038 30071234

28. Miller CA, Fildes JE, Ray SG, Doran H, Yonan N, Williams SG, et al. Non-invasive approaches for the diagnosis of acute cardiac allograft rejection. Heart (British Cardiac Society). 2013;99(7):445–53

29. Mavrogeni SI, Athanasopoulos G, Gouziouta A, Leontiadis E, Adamopoulos S, Kolovou G. Cardiac transplantation: towards a new noninvasive approach of cardiac allograft rejection. Expert review of cardiovascular therapy. 2017;15(4):307–13 doi: 10.1080/14779072.2017.1307734 28317398

30. Phillips M, Boehmer JP, Cataneo RN, Cheema T, Eisen HJ, Fallon JT, et al. Heart allograft rejection: detection with breath alkanes in low levels (the HARDBALL study). The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 2004;23(6):701–8

31. Phillips M, Boehmer JP, Cataneo RN, Cheema T, Eisen HJ, Fallon JT, et al. Prediction of heart transplant rejection with a breath test for markers of oxidative stress. The American journal of cardiology. 2004;94(12):1593–4 doi: 10.1016/j.amjcard.2004.08.052 15589029

32. Deng MC, Eisen HJ, Mehra MR, Billingham M, Marboe CC, Berry G, et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2006;6(1):150–60

33. Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Deng MC, Cappola TP, et al. Gene-expression profiling for rejection surveillance after cardiac transplantation. The New England journal of medicine. 2010;362(20):1890–900 doi: 10.1056/NEJMoa0912965 20413602

34. Yamani MH, Taylor DO, Rodriguez ER, Cook DJ, Zhou L, Smedira N, et al. Transplant vasculopathy is associated with increased AlloMap gene expression score. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 2007;26(4):403–6

35. Starling RC, Pham M, Valantine H, Miller L, Eisen H, Rodriguez ER, et al. Molecular testing in the management of cardiac transplant recipients: initial clinical experience. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 2006;25(12):1389–95

36. Gupta D, Bartra S, Shih R, Breault LM, Bleiweis MS, Fricker FJ, et al. Correlation of Allomap Scores in Pediatric Heart Transplant Recipients: Are We Ready to Apply This to Our Patients? The Journal of Heart and Lung Transplantation. 2017;36(4):S267

37. Garcia Moreira V, Prieto Garcia B, Baltar Martin JM, Ortega Suarez F, Alvarez FV. Cell-free DNA as a noninvasive acute rejection marker in renal transplantation. Clinical chemistry. 2009;55(11):1958–66 doi: 10.1373/clinchem.2009.129072 19729469

38. Snyder TM, Khush KK, Valantine HA, Quake SR. Universal noninvasive detection of solid organ transplant rejection. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(15):6229–34. doi: 10.1073/pnas.1013924108 21444804

39. Hidestrand M, Tomita-Mitchell A, Hidestrand PM, Oliphant A, Goetsch M, Stamm K, et al. Highly sensitive noninvasive cardiac transplant rejection monitoring using targeted quantification of donor-specific cell-free deoxyribonucleic acid. Journal of the American College of Cardiology. 2014;63(12):1224–6. doi: 10.1016/j.jacc.2013.09.029 24140666

40. Lo YM, Chan KC, Sun H, Chen EZ, Jiang P, Lun FM, et al. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Science translational medicine. 2010;2(61):61ra91 doi: 10.1126/scitranslmed.3001720 21148127

41. Ghanta S, Mitchell ME, Ames M, Hidestrand M, Simpson P, Goetsch M, et al. Non-invasive prenatal detection of trisomy 21 using tandem single nucleotide polymorphisms. PloS one. 2010;5(10):e13184. doi: 10.1371/journal.pone.0013184 20949031

42. Jeanty C, Derderian SC, Mackenzie TC. Maternal-fetal cellular trafficking: clinical implications and consequences. Current opinion in pediatrics. 2014;26(3):377–82. doi: 10.1097/MOP.0000000000000087 24759226

43. Yong E. Cancer biomarkers: Written in blood. Nature. 2014;511(7511):524–6 doi: 10.1038/511524a 25079538

44. Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S, et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(45):16368–73. doi: 10.1073/pnas.0507904102 16258065

45. Sacher AG, Paweletz C, Dahlberg SE, Alden RS, O'Connell A, Feeney N, et al. Prospective Validation of Rapid Plasma Genotyping for the Detection of EGFR and KRAS Mutations in Advanced Lung Cancer. JAMA oncology. 2016;2(8):1014–22. doi: 10.1001/jamaoncol.2016.0173 27055085

46. Kodahl AR, Ehmsen S, Pallisgaard N, Jylling AMB, Jensen JD, Laenkholm AV, et al. Correlation between circulating cell-free PIK3CA tumor DNA levels and treatment response in patients with PIK3CA-mutated metastatic breast cancer. Molecular oncology. 2018;12(6):925–35. doi: 10.1002/1878-0261.12305 29689598

47. Zhang L, Liang Y, Li S, Zeng F, Meng Y, Chen Z, et al. The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis. Molecular cancer. 2019;18(1):36. doi: 10.1186/s12943-019-0989-z 30849971

48. Mandel P, Metais P. Les acides nucléiques du plasma sanguine chez l’homme. Comptes rendus des seances de la Societe de biologie et de ses filiales. 1948;142(3–4):241–3 18875018

49. Nagata S, Nagase H, Kawane K, Mukae N, Fukuyama H. Degradation of chromosomal DNA during apoptosis. Cell death and differentiation. 2003;10(1):108–16 doi: 10.1038/sj.cdd.4401161 12655299

50. Stroun M, Lyautey J, Lederrey C, Mulcahy HE, Anker P. Alu repeat sequences are present in increased proportions compared to a unique gene in plasma/serum DNA: evidence for a preferential release from viable cells? Annals of the New York Academy of Sciences. 2001;945:258–64 doi: 10.1111/j.1749-6632.2001.tb03894.x 11708488

51. Meddeb R, Dache ZAA, Thezenas S, Otandault A, Tanos R, Pastor B, et al. Quantifying circulating cell-free DNA in humans. Scientific reports. 2019;9(1):5220. doi: 10.1038/s41598-019-41593-4 30914716

52. Thierry AR, El Messaoudi S, Gahan PB, Anker P, Stroun M. Origins, structures, and functions of circulating DNA in oncology. Cancer metastasis reviews. 2016;35(3):347–76. doi: 10.1007/s10555-016-9629-x 27392603

53. Aucamp J, Bronkhorst AJ, Badenhorst CPS, Pretorius PJ. The diverse origins of circulating cell-free DNA in the human body: a critical re-evaluation of the literature. Biological reviews of the Cambridge Philosophical Society. 2018;93(3):1649–83 doi: 10.1111/brv.12413 29654714

54. Lo YM, Rainer TH, Chan LY, Hjelm NM, Cocks RA. Plasma DNA as a prognostic marker in trauma patients. Clinical chemistry. 2000;46(3):319–23 10702517

55. Rainer TH, Wong LK, Lam W, Yuen E, Lam NY, Metreweli C, et al. Prognostic use of circulating plasma nucleic acid concentrations in patients with acute stroke. Clinical chemistry. 2003;49(4):562–9 doi: 10.1373/49.4.562 12651807

56. Tug S, Helmig S, Menke J, Zahn D, Kubiak T, Schwarting A, et al. Correlation between cell free DNA levels and medical evaluation of disease progression in systemic lupus erythematosus patients. Cellular immunology. 2014;292(1–2):32–9 doi: 10.1016/j.cellimm.2014.08.002 25243646

57. Ahmed AI, Soliman RA, Samir S. Cell Free DNA and Procalcitonin as Early Markers of Complications in ICU Patients with Multiple Trauma and Major Surgery. Clinical laboratory. 2016;62(12):2395–404 doi: 10.7754/Clin.Lab.2016.160615 28164563

58. Vajpeyee A, Wijatmiko T, Vajpeyee M, Taywade O. Cell free DNA: A Novel Predictor of Neurological Outcome after Intravenous Thrombolysis and/or Mechanical Thrombectomy in Acute Ischemic Stroke Patients. Neurointervention. 2018;13(1):13–9. doi: 10.5469/neuroint.2018.13.1.13 29535894

59. Duvvuri B, Lood C. Cell-Free DNA as a Biomarker in Autoimmune Rheumatic Diseases. Frontiers in immunology. 2019;10:502. doi: 10.3389/fimmu.2019.00502 30941136

60. Haller N, Helmig S, Taenny P, Petry J, Schmidt S, Simon P. Circulating, cell-free DNA as a marker for exercise load in intermittent sports. PloS one. 2018;13(1):e0191915. doi: 10.1371/journal.pone.0191915 29370268

61. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, et al. Presence of fetal DNA in maternal plasma and serum. Lancet (London, England). 1997;350(9076):485–7

62. Lo YM, Zhang J, Leung TN, Lau TK, Chang AM, Hjelm NM. Rapid clearance of fetal DNA from maternal plasma. American journal of human genetics. 1999;64(1):218–24. doi: 10.1086/302205 9915961

63. Khier S, Lohan L. Kinetics of circulating cell-free DNA for biomedical applications: critical appraisal of the literature. Future science OA. 2018;4(4):Fso295. doi: 10.4155/fsoa-2017-0140 29682327

64. Lui YY, Chik KW, Chiu RW, Ho CY, Lam CW, Lo YM. Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation. Clinical chemistry. 2002;48(3):421–7 11861434

65. Macher HC, Suarez-Artacho G, Guerrero JM, Gomez-Bravo MA, Alvarez-Gomez S, Bernal-Bellido C, et al. Monitoring of transplanted liver health by quantification of organ-specific genomic marker in circulating DNA from receptor. PloS one.

66. Ragalie WS, Stamm K, Mahnke D, Liang HL, Simpson P, Katz R, et al. Noninvasive Assay for Donor Fraction of Cell-Free DNA in Pediatric Heart Transplant Recipients. Journal of the American College of Cardiology. 2018;71(25):2982–3 doi: 10.1016/j.jacc.2018.04.026 29929623

67. De Vlaminck I, Martin L, Kertesz M, Patel K, Kowarsky M, Strehl C, et al. Noninvasive monitoring of infection and rejection after lung transplantation. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(43):13336–41. doi: 10.1073/pnas.1517494112 26460048

68. De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, et al. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Science translational medicine. 2014;6(241):241ra77. doi: 10.1126/scitranslmed.3007803 24944192

69. Khush KK, Patel J, Pinney S, Kao A, Alharethi R, DePasquale E, et al. Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2019

70. Bloom RD, Bromberg JS, Poggio ED, Bunnapradist S, Langone AJ, Sood P, et al. Cell-Free DNA and Active Rejection in Kidney Allografts. Journal of the American Society of Nephrology: JASN. 2017;28(7):2221–32. doi: 10.1681/ASN.2016091034 28280140

71. Gielis EM, Beirnaert C, Dendooven A, Meysman P, Laukens K, De Schrijver J, et al. Plasma donor-derived cell-free DNA kinetics after kidney transplantation using a single tube multiplex PCR assay. PloS one. 2018;13(12):e0208207. doi: 10.1371/journal.pone.0208207 30521549

72. Huang E, Sethi S, Peng A, Najjar R, Mirocha J, Haas M, et al. Early clinical experience using donor-derived cell-free DNA to detect rejection in kidney transplant recipients. Am J Transplant. 2019;19(6):1663–1670. doi: 10.1111/ajt.15289 30725531

73. Schutz E, Fischer A, Beck J, Harden M, Koch M, Wuensch T, et al. Graft-derived cell-free DNA, a noninvasive early rejection and graft damage marker in liver transplantation: A prospective, observational, multicenter cohort study. PLoS Med. 2017;14(4)

74. Grskovic M, Hiller DJ, Eubank LA, Sninsky JJ, Christopherson C, Collins JP, et al. Validation of a Clinical-Grade Assay to Measure Donor-Derived Cell-Free DNA in Solid Organ Transplant Recipients. The Journal of molecular diagnostics: JMD. 2016;18(6):890–902 doi: 10.1016/j.jmoldx.2016.07.003 27727019

75. Beck J, Bierau S, Balzer S, Andag R, Kanzow P, Schmitz J, et al. Digital droplet PCR for rapid quantification of donor DNA in the circulation of transplant recipients as a potential universal biomarker of graft injury. Clinical chemistry. 2013;59(12):1732–41 doi: 10.1373/clinchem.2013.210328 24061615

76. Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285 doi: 10.1038/nature19057 27535533

77. Karczewski KJ FL, Tiao G, Cummings BB, Alfoldi J, Wang G et al. Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes. Cold Spring Harbor Laboratory bioRxiv. 2019

78. Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68–74. doi: 10.1038/nature15393 26432245

79. Tomita-Mitchell A, Mahnke DK, Struble CA, Tuffnell ME, Stamm KD, Hidestrand M, et al. Human gene copy number spectra analysis in congenital heart malformations. Physiological genomics. 2012;44(9):518–41. doi: 10.1152/physiolgenomics.00013.2012 22318994

80. Landrum MJ, Kattman BL. ClinVar at five years: Delivering on the promise. Human mutation. 2018;39(11):1623–30 doi: 10.1002/humu.23641 30311387

81. Amberger JS, Bocchini CA, Scott AF, Hamosh A. OMIM.org: leveraging knowledge across phenotype-gene relationships. Nucleic acids research. 2019;47(D1):D1038–d43. doi: 10.1093/nar/gky1151 30445645

82. Cha RS, Zarbl H, Keohavong P, Thilly WG. Mismatch amplification mutation assay (MAMA): application to the c-H-ras gene. PCR methods and applications. 1992;2(1):14–20 doi: 10.1101/gr.2.1.14 1490171

83. Umetani N, Kim J, Hiramatsu S, Reber HA, Hines OJ, Bilchik AJ, et al. Increased integrity of free circulating DNA in sera of patients with colorectal or periampullary cancer: direct quantitative PCR for ALU repeats. Clinical chemistry. 2006;52(6):1062–9 doi: 10.1373/clinchem.2006.068577 16723681

84. Hwu HR, Roberts JW, Davidson EH, Britten RJ. Insertion and/or deletion of many repeated DNA sequences in human and higher ape evolution. Proceedings of the National Academy of Sciences of the United States of America. 1986;83(11):3875–9. doi: 10.1073/pnas.83.11.3875 3012536

85. Gu Z, Wang H, Nekrutenko A, Li WH. Densities, length proportions, and other distributional features of repetitive sequences in the human genome estimated from 430 megabases of genomic sequence. Gene. 2000;259(1–2):81–8 doi: 10.1016/s0378-1119(00)00434-0 11163965

86. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921 doi: 10.1038/35057062 11237011

87. Bronkhorst AJ, Ungerer V, Holdenrieder S. The emerging role of cell-free DNA as a molecular marker for cancer management. Biomolecular detection and quantification. 2019;17:100087.

88. Kindell S, Ragalie W, Zangwill S, Katz R, Tomita-Mitchell A, Stamm K, et al. Early Changes in Donor Fraction Cell-free DNA in Newly Transplanted Pediatric Heart Transplant Patients. The Journal of Heart and Lung Transplantation. 2018;37(4):S400

89. Richmond ME, Kindel SJ, Schroder JN, Deshpande SR, Bichell DP, Wigger MA, et al. Increase in Donor Fraction Cell-Free DNA Correlates with Cellular and Antibody Mediated Rejection (ACR/AMR) in Adult and Pediatric Heart Transplant Recipients: DNA Based Transplant Rejection Test (DTRT)-A Prospective Blinded Multicenter NIH/NHLBI Funded Clinical Study. The Journal of Heart and Lung Transplantation. 2019;38(4):S50

90. Zangwill S, Kindel S. J., Schroder J. N., Bichell D. P., Deshpande S. R., Wigger M. A., Richmond M. E., Knecht K. R., Gaglianello N. A., Pahl E., Simpson P. M., Mahle W. T., Mitchell A. T., Mitchell M. E. Increase in Total Cell-Free DNA Correlates with Death in Adult and Pediatric Heart Transplant Recipients: DNA Based Transplant Rejection Test (DTRT)-A Prospective Blinded Multicenter NIH/NHLBI Funded Clinical Study. JACC 2019. 2019

91. Clinical and Laboratory Standards Institute (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures: Approved Guideline. CLSI document EP17-A2. ed 2. Wayne, PA, Clinical and Laboratory Standards Institute, 2012.

92. Clinical and Laboratory Standards Institute (CLSI). Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach: Approved Guideline. CLSI document EP06-A. Wayne, PA, Clinical and Laboratory Standards Institute; 2003.

93. Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry: Approved Guideline. CLSI document EP07-A2. Ed 2. Wayne, PA: Clinical and Laboratory Standards Institute; 2005.

94. Chiu RW, Poon LL, Lau TK, Leung TN, Wong EM, Lo YM. Effects of blood-processing protocols on fetal and total DNA quantification in maternal plasma. Clinical chemistry. 2001;47(9):1607–13 11514393

95. El Messaoudi S, Rolet F, Mouliere F, Thierry AR. Circulating cell free DNA: Preanalytical considerations. Clinica chimica acta; international journal of clinical chemistry. 2013;424:222–30 doi: 10.1016/j.cca.2013.05.022 23727028

96. Sherwood JL, Corcoran C, Brown H, Sharpe AD, Musilova M, Kohlmann A. Optimised Pre-Analytical Methods Improve KRAS Mutation Detection in Circulating Tumour DNA (ctDNA) from Patients with Non-Small Cell Lung Cancer (NSCLC). PloS one. 2016;11(2):e0150197. doi: 10.1371/journal.pone.0150197 26918901

97. Grolz D, Hauch S, Schlumpberger M, Guenther K, Voss T, Sprenger-Haussels M, et al. Liquid Biopsy Preservation Solutions for Standardized Pre-Analytical Workflows-Venous Whole Blood and Plasma. Current pathobiology reports. 2018;6(4):275–86. doi: 10.1007/s40139-018-0180-z 30595972

98. Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer research. 2001;61(4):1659–65 11245480

99. Lun FM, Chiu RW, Chan KC, Leung TY, Lau TK, Lo YM. Microfluidics digital PCR reveals a higher than expected fraction of fetal DNA in maternal plasma. Clinical chemistry. 2008;54(10):1664–72 doi: 10.1373/clinchem.2008.111385 18703764

100. Parpart-Li S, Bartlett B, Popoli M, Adleff V, Tucker L, Steinberg R, et al. The Effect of Preservative and Temperature on the Analysis of Circulating Tumor DNA. Clinical cancer research: an official journal of the American Association for Cancer Research. 2017;23(10):2471–7

101. Chan KC, Yeung SW, Lui WB, Rainer TH, Lo YM. Effects of preanalytical factors on the molecular size of cell-free DNA in blood. Clinical chemistry. 2005;51(4):781–4 doi: 10.1373/clinchem.2004.046219 15708950

102. Norton SE, Luna KK, Lechner JM, Qin J, Fernando MR. A new blood collection device minimizes cellular DNA release during sample storage and shipping when compared to a standard device. Journal of clinical laboratory analysis. 2013;27(4):305–11. doi: 10.1002/jcla.21603 23852790

103. Denis MG, Knol AC, Theoleyre S, Vallee A, Dreno B. Efficient Detection of BRAF Mutation in Plasma of Patients after Long-term Storage of Blood in Cell-Free DNA Blood Collection Tubes. Clinical chemistry. 2015;61(6):886–8 doi: 10.1373/clinchem.2015.238352 25896990

104. Toro PV, Erlanger B, Beaver JA, Cochran RL, VanDenBerg DA, Yakim E, et al. Comparison of cell stabilizing blood collection tubes for circulating plasma tumor DNA. Clinical biochemistry. 2015;48(15):993–8. doi: 10.1016/j.clinbiochem.2015.07.097 26234639

105. Kang Q, Henry NL, Paoletti C, Jiang H, Vats P, Chinnaiyan AM, et al. Comparative analysis of circulating tumor DNA stability In K3EDTA, Streck, and CellSave blood collection tubes. Clinical biochemistry. 2016;49(18):1354–60 doi: 10.1016/j.clinbiochem.2016.03.012 27129799

106. Meddeb R, Pisareva E, Thierry AR. Guidelines for the Preanalytical Conditions for Analyzing Circulating Cell-Free DNA. Clinical chemistry. 2019;65(5):623–33 doi: 10.1373/clinchem.2018.298323 30792266

107. Trigg RM, Martinson LJ, Parpart-Li S, Shaw JA. Factors that influence quality and yield of circulating-free DNA: A systematic review of the methodology literature. Heliyon. 2018;4(7):e00699. doi: 10.1016/j.heliyon.2018.e00699 30094369

108. Nikolaev S, Lemmens L, Koessler T, Blouin JL, Nouspikel T. Circulating tumoral DNA: Preanalytical validation and quality control in a diagnostic laboratory. Analytical biochemistry. 2018;542:34–9 doi: 10.1016/j.ab.2017.11.004 29137972

109. Fernando MR, Jiang C, Krzyzanowski GD, Ryan WL. New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes. PloS one. 2017;12(8):e0183915. doi: 10.1371/journal.pone.0183915 28850588

110. Dhallan R, Au WC, Mattagajasingh S, Emche S, Bayliss P, Damewood M, et al. Methods to increase the percentage of free fetal DNA recovered from the maternal circulation. Jama. 2004;291(9):1114–9 doi: 10.1001/jama.291.9.1114 14996781

111. Zhang Y, Li Q, Hui N, Fei M, Hu Z, Sun S. Effect of formaldehyde treatment on the recovery of cell-free fetal DNA from maternal plasma at different processing times. Clinica chimica acta; international journal of clinical chemistry. 2008;397(1–2):60–4 doi: 10.1016/j.cca.2008.07.017 18692490

112. Srinivasan M, Sedmak D, Jewell S. Effect of fixatives and tissue processing on the content and integrity of nucleic acids. The American journal of pathology. 2002;161(6):1961–71. doi: 10.1016/S0002-9440(10)64472-0 12466110

113. Hidestrand M, Stokowski R, Song K, Oliphant A, Deavers J, Goetsch M, et al. Influence of temperature during transportation on cell-free DNA analysis. Fetal diagnosis and therapy. 2012;31(2):122–8 doi: 10.1159/000335020 22261730

114. Medina Diaz I, Nocon A, Mehnert DH, Fredebohm J, Diehl F, Holtrup F. Performance of Streck cfDNA Blood Collection Tubes for Liquid Biopsy Testing. PloS one. 2016;11(11):e0166354. doi: 10.1371/journal.pone.0166354 27832189

115. Cell-Free DNA BCT®: Instructions for Use, Streck, La Vista, NE, USA, 350547–9, 2016–08. https://www.streck.com/wp-content/uploads/2017/01/01_IFU_Cell-Free_DNA_BCT_IFU.pdf

116. Warton K, Yuwono NL, Cowley MJ, McCabe MJ, So A, Ford CE. Evaluation of Streck BCT and PAXgene Stabilised Blood Collection Tubes for Cell-Free Circulating DNA Studies in Plasma. Molecular diagnosis & therapy. 2017;21(5):563–70

117. Feingold B, Irving C, Tatum GH, Webber SA. Prognostic significance of recurrent grade 1B rejection in the first year after pediatric cardiac transplantation: a case for reinstatement of the 1B rejection grade. Pediatric transplantation. 2011;15(6):589–93. doi: 10.1111/j.1399-3046.2011.01530.x 21884346

118. Peled Y, Lavee J, Ram E, Kassif Y, Peled A, Freimark D, et al. Recurrent acute cellular rejection graded ISHLT 1R early after heart transplantation negatively affects long-term outcomes: The prognostic significance of 1990 ISHLT grades 1B and 2. Transplant immunology. 2019

119. Zangwill SD, Stamm KD, Hidestrand M, Tomita-Mitchell A, Mitchell ME. Effect of Endomyocardial Biopsy on Levels of Donor Specific Cell-Free DNA. The Journal of Heart and Lung Transplantation. https://doi.org/10.1016/j.healun.2019.06.005


Článek vyšel v časopise

PLOS One


2020 Číslo 1