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ctDNA and Lung Cancer

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Circulating Tumor Cells

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

The discovery of cell-free DNA (cfDNA) in biofluids such as blood, saliva, urine, and pleural fluid has broadened our understanding of extracellular genomic biology and is enabling a variety of important clinical applications. The promise of clinical utility has fueled efforts both to understand the physiologic underpinnings of cfDNA and to broaden the repertoire of cancer-associated signals being queried. Although the field initially focused primarily on measurement of cancer-associated mutations in cell-free DNA, recent years have seen tremendous progress in the characterization of other cancer-associated DNA features such as methylation, fragment length, nucleosome positioning, and strandedness. These advances are driving the development of diagnostic technologies for treatment selection, therapy monitoring, assessment of minimal residual disease, and early cancer detection. This chapter will review the landscape of cfDNA biology and the scientific and technological advances for the assessment of cfDNA, with a particular focus on non-small cell lung cancer as a clinical model.

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References

  1. Abbosh C, Birkbak NJ, Wilson GA, et al (2017) Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 545:446–451. https://doi.org/10.1038/nature22364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Adalsteinsson VA, Ha G, Freeman SS, et al (2017) Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nat Commun 8:1324. https://doi.org/10.1038/s41467-017-00965-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Adams DH, Diaz N, Gahan PB (1997) In vitro stimulation by tumour cell media of [3H]-thymidine incorporation by mouse spleen lymphocytes. Cell Biochem Funct 15:119–126. https://doi.org/10.1002/(SICI)1099-0844(19970601)15:2<119::AID-CBF731>3.0.CO;2-C

    Article  CAS  PubMed  Google Scholar 

  4. Adams DH, McIntosh AA (1985) Studies on the cytosolic DNA of chick embryo fibroblasts and its uptake by recipient cultured cells. Int J Biochem 17:1041–1051. https://doi.org/10.1016/0020-711x(85)90035-7

    Article  CAS  PubMed  Google Scholar 

  5. Anagnostou V, Bruhm DC, Niknafs N, et al (2020) Integrative Tumor and Immune Cell Multi-omic Analyses Predict Response to Immune Checkpoint Blockade in Melanoma. Cell Rep Med 1:100139. https://doi.org/10.1016/j.xcrm.2020.100139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Arpinati L, Shaul ME, Kaisar-Iluz N, et al (2020) NETosis in cancer: a critical analysis of the impact of cancer on neutrophil extracellular trap (NET) release in lung cancer patients vs. mice. Cancer Immunol Immunother CII 69:199–213. https://doi.org/10.1007/s00262-019-02474-x

    Article  CAS  PubMed  Google Scholar 

  7. Balaj L, Lessard R, Dai L, et al (2011) Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2:180. https://doi.org/10.1038/ncomms1180

    Article  CAS  PubMed  Google Scholar 

  8. Berensmeier S (2006) Magnetic particles for the separation and purification of nucleic acids. Appl Microbiol Biotechnol 73:495–504. https://doi.org/10.1007/s00253-006-0675-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bettegowda C, Sausen M, Leary RJ, et al (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6:224ra24. https://doi.org/10.1126/scitranslmed.3007094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Black RC, Khurshid H (2015) NSCLC: An Update of Driver Mutations, Their Role in Pathogenesis and Clinical Significance. R I Med J 2013 98:25–28

    Google Scholar 

  11. Boskovic T, Stanic J, Pena-Karan S, et al (2014) Pneumothorax after transthoracic needle biopsy of lung lesions under CT guidance. J Thorac Dis 6:S99–S107. https://doi.org/10.3978/j.issn.2072-1439.2013.12.08

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bray F, Ferlay J, Soerjomataram I, et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492

    Article  PubMed  Google Scholar 

  13. Bronkhorst AJ, Ungerer V, Diehl F, et al (2021) Towards systematic nomenclature for cell-free DNA. Hum Genet 140:565–578. https://doi.org/10.1007/s00439-020-02227-2

    Article  CAS  PubMed  Google Scholar 

  14. Bryzgunova OE, Tamkovich SN, Cherepanova AV, et al (2015) Redistribution of Free- and Cell-Surface-Bound DNA in Blood of Benign and Malignant Prostate Tumor Patients. Acta Naturae 7:115–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Burnham P, Kim MS, Agbor-Enoh S, et al (2016) Single-stranded DNA library preparation uncovers the origin and diversity of ultrashort cell-free DNA in plasma. Sci Rep 6. https://doi.org/10.1038/srep27859

  16. Chan KCA, Jiang P, Chan CWM, et al (2013) Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing. Proc Natl Acad Sci U S A 110:18761–18768. https://doi.org/10.1073/pnas.1313995110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chaudhuri AA, Chabon JJ, Lovejoy AF, et al (2017) Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling. Cancer Discov 7:1394–1403. https://doi.org/10.1158/2159-8290.CD-17-0716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chelobanov BP, Laktionov PP, Vlasov VV (2006) Proteins involved in binding and cellular uptake of nucleic acids. Biochem Biokhimiia 71:583–596. https://doi.org/10.1134/s0006297906060010

    Article  CAS  Google Scholar 

  19. Cheng J, Morselli M, Huang W-L, et al (2021a) Plasma Contains Ultra-short Single-stranded DNA in Addition to Nucleosomal cfDN

    Google Scholar 

  20. Cheng LY, Dai P, Wu LR, Zhang DY (2021b) Direct capture and sequencing reveal ultra-short single-stranded DNA in biofluids

    Google Scholar 

  21. Cheng THT, Lui KO, Peng XL, et al (2018) DNase1 Does Not Appear to Play a Major Role in the Fragmentation of Plasma DNA in a Knockout Mouse Model. Clin Chem 64:406–408. https://doi.org/10.1373/clinchem.2017.280446

    Article  CAS  PubMed  Google Scholar 

  22. Chi A, Chen H, Wen S, et al (2017) Comparison of particle beam therapy and stereotactic body radiotherapy for early stage non-small cell lung cancer: A systematic review and hypothesis-generating meta-analysis. Radiother Oncol J Eur Soc Ther Radiol Oncol 123:346–354. https://doi.org/10.1016/j.radonc.2017.05.007

    Article  Google Scholar 

  23. Chiu RWK, Chan LYS, Lam NYL, et al (2003) Quantitative analysis of circulating mitochondrial DNA in plasma. Clin Chem 49:719–726. https://doi.org/10.1373/49.5.719

    Article  CAS  PubMed  Google Scholar 

  24. Christensen E, Birkenkamp-Demtröder K, Sethi H, et al (2019) Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma. J Clin Oncol Off J Am Soc Clin Oncol 37:1547–1557. https://doi.org/10.1200/JCO.18.02052

    Article  CAS  Google Scholar 

  25. Cohen JD, Douville C, Dudley JC, et al (2021) Detection of low-frequency DNA variants by targeted sequencing of the Watson and Crick strands. Nat Biotechnol 1–8. https://doi.org/10.1038/s41587-021-00900-z

  26. Cohen JD, Li L, Wang Y, et al (2018) Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science eaar3247. https://doi.org/10.1126/science.aar3247

  27. Cools-Lartigue J, Spicer J, McDonald B, et al (2013) Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest. https://doi.org/10.1172/JCI67484

  28. Coombes RC, Page K, Salari R, et al (2019) Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence. Clin Cancer Res Off J Am Assoc Cancer Res 25:4255–4263. https://doi.org/10.1158/1078-0432.CCR-18-3663

    Article  CAS  Google Scholar 

  29. Cristiano S, Leal A, Phallen J, et al (2019) Genome-wide cell-free DNA fragmentation in patients with cancer. Nature 1. https://doi.org/10.1038/s41586-019-1272-6

  30. Cui S, Zhang W, Xiong L, et al (2016) Use of capture-based next-generation sequencing to detect ALK fusion in plasma cell-free DNA of patients with non-small-cell lung cancer. Oncotarget 8:2771–2780. https://doi.org/10.18632/oncotarget.13741

    Article  PubMed Central  Google Scholar 

  31. Curran WJ, Paulus R, Langer CJ, et al (2011) Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst 103:1452–1460. https://doi.org/10.1093/jnci/djr325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. de Bont CM, Boelens WC, Pruijn GJM (2019) NETosis, complement, and coagulation: a triangular relationship. Cell Mol Immunol 16:19–27. https://doi.org/10.1038/s41423-018-0024-0

    Article  CAS  PubMed  Google Scholar 

  33. Demuth C, Madsen AT, Weber B, et al (2018) The T790M resistance mutation in EGFR is only found in cfDNA from erlotinib-treated NSCLC patients that harbored an activating EGFR mutation before treatment. BMC Cancer 18:191. https://doi.org/10.1186/s12885-018-4108-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Diaz LA, Bardelli A (2014) Liquid Biopsies: Genotyping Circulating Tumor DNA. J Clin Oncol 32:579–586. https://doi.org/10.1200/JCO.2012.45.2011

    Article  PubMed  PubMed Central  Google Scholar 

  35. Emlen W, Mannik M (1978) Kinetics and mechanisms for removal of circulating single-stranded DNA in mice. J Exp Med 147:684–699. https://doi.org/10.1084/jem.147.3.684

    Article  CAS  PubMed  Google Scholar 

  36. Emlen W, Mannik M (1984) Effect of DNA size and strandedness on the in vivo clearance and organ localization of DNA. Clin Exp Immunol 56:185–192

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Esteller M (2008) Epigenetics in cancer. N Engl J Med 358:1148–1159. https://doi.org/10.1056/NEJMra072067

    Article  CAS  PubMed  Google Scholar 

  38. Ettinger DS, Wood DE, Aisner DL, et al (2017) Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 15:504–535. https://doi.org/10.6004/jnccn.2017.0050

    Article  PubMed  Google Scholar 

  39. Fan HC, Blumenfeld YJ, Chitkara U, et al (2008) Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci 105:16266–16271. https://doi.org/10.1073/pnas.0808319105

    Article  PubMed  PubMed Central  Google Scholar 

  40. Farago AF, Taylor MS, Doebele RC, et al (2018) Clinicopathologic Features of Non-Small-Cell Lung Cancer Harboring an NTRK Gene Fusion. JCO Precis Oncol 2018. https://doi.org/10.1200/PO.18.00037

  41. Fernando MR, Jiang C, Krzyzanowski GD, Ryan WL (2017) New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes. PLOS ONE 12:e0183915. https://doi.org/10.1371/journal.pone.0183915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fleischhacker M, Schmidt B, Weickmann S, et al (2011) Methods for isolation of cell-free plasma DNA strongly affect DNA yield. Clin Chim Acta Int J Clin Chem 412:2085–2088. https://doi.org/10.1016/j.cca.2011.07.011

    Article  CAS  Google Scholar 

  43. Fuchs TA, Brill A, Duerschmied D, et al (2010) Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A 107:15880–15885. https://doi.org/10.1073/pnas.1005743107

    Article  PubMed  PubMed Central  Google Scholar 

  44. Gaffney DJ, McVicker G, Pai AA, et al (2012) Controls of Nucleosome Positioning in the Human Genome. PLOS Genet 8:e1003036. https://doi.org/10.1371/journal.pgen.1003036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gainor JF, Dardaei L, Yoda S, et al (2016) Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer. Cancer Discov 6:1118–1133. https://doi.org/10.1158/2159-8290.CD-16-0596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gale D, Lawson ARJ, Howarth K, et al (2018) Development of a highly sensitive liquid biopsy platform to detect clinically-relevant cancer mutations at low allele fractions in cell-free DNA. PloS One 13:e0194630. https://doi.org/10.1371/journal.pone.0194630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gandara DR, Paul SM, Kowanetz M, et al (2018) Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nat Med 24:1441–1448. https://doi.org/10.1038/s41591-018-0134-3

    Article  CAS  PubMed  Google Scholar 

  48. Gansauge M-T, Meyer M (2013) Single-stranded DNA library preparation for the sequencing of ancient or damaged DNA. Nat Protoc 8:737–748. https://doi.org/10.1038/nprot.2013.038

    Article  CAS  PubMed  Google Scholar 

  49. Goldberg SB, Narayan A, Kole AJ, et al (2018) Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA. Clin Cancer Res Off J Am Assoc Cancer Res 24:1872–1880. https://doi.org/10.1158/1078-0432.CCR-17-1341

    Article  CAS  Google Scholar 

  50. Gosse C, Pecq JBL, Defrance P, Paoletti C (1965) Initial Degradation of Deoxyribonucleic Acid after Injection in Mammals. Cancer Res 25:877–883

    CAS  PubMed  Google Scholar 

  51. Guescini M, Genedani S, Stocchi V, Agnati LF (2010) Astrocytes and Glioblastoma cells release exosomes carrying mtDNA. J Neural Transm Vienna Austria 1996 117:1–4. https://doi.org/10.1007/s00702-009-0288-8

  52. Han DSC, Ni M, Chan RWY, et al (2020) The Biology of Cell-free DNA Fragmentation and the Roles of DNASE1, DNASE1L3, and DFFB. Am J Hum Genet 106:202–214. https://doi.org/10.1016/j.ajhg.2020.01.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Heerink WJ, de Bock GH, de Jonge GJ, et al (2017) Complication rates of CT-guided transthoracic lung biopsy: meta-analysis. Eur Radiol 27:138–148. https://doi.org/10.1007/s00330-016-4357-8

    Article  CAS  PubMed  Google Scholar 

  54. Herbst RS, Morgensztern D, Boshoff C (2018) The biology and management of non-small cell lung cancer. Nature 553:446–454. https://doi.org/10.1038/nature25183

    Article  CAS  PubMed  Google Scholar 

  55. Hisano O, Ito T, Miura F (2021) Short single-stranded DNAs with putative non-canonical structures comprise a new class of plasma cell-free DNA. BMC Biol 19:225. https://doi.org/10.1186/s12915-021-01160-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Huang C-Y, Chen Y-M, Wu C-H, et al (2014) Circulating free mitochondrial DNA concentration and its association with erlotinib treatment in patients with adenocarcinoma of the lung. Oncol Lett 7:2180–2184. https://doi.org/10.3892/ol.2014.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hudecova I, Smith CG, Hänsel-Hertsch R, et al (2021) Characteristics, origin, and potential for cancer diagnostics of ultrashort plasma cell-free DNA. Genome Res. https://doi.org/10.1101/gr.275691.121

  58. Hummel EM, Hessas E, Müller S, et al (2018) Cell-free DNA release under psychosocial and physical stress conditions. Transl Psychiatry 8:1–10. https://doi.org/10.1038/s41398-018-0264-x

    Article  CAS  Google Scholar 

  59. Jahr S, Hentze H, Englisch S, et al (2001) DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 61:1659–1665

    CAS  PubMed  Google Scholar 

  60. Jia Y, Yun C-H, Park E, et al (2016) Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature 534:129–132. https://doi.org/10.1038/nature17960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Jiang P, Xie T, Ding SC, et al (2020) Detection and characterization of jagged ends of double-stranded DNA in plasma. Genome Res 30:1144–1153. https://doi.org/10.1101/gr.261396.120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13:484–492. https://doi.org/10.1038/nrg3230

    Article  CAS  PubMed  Google Scholar 

  63. Kahlert C, Melo SA, Protopopov A, et al (2014) Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J Biol Chem 289:3869–3875. https://doi.org/10.1074/jbc.C113.532267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kakarla R, Hur J, Kim YJ, et al (2020) Apoptotic cell-derived exosomes: messages from dying cells. Exp Mol Med 52:1–6. https://doi.org/10.1038/s12276-019-0362-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kaplan MJ, Radic M (2012) Neutrophil extracellular traps: double-edged swords of innate immunity. J Immunol Baltim Md 1950 189:2689–2695. https://doi.org/10.4049/jimmunol.1201719

  66. Karp A, Isaac PG, Ingram DS (1998) Isolation of Nucleic Acids Using Silica-Gel Based Membranes: Methods Based on the Use of QIAamp Spin Columns. In: Karp A, Isaac PG, Ingram DS (eds) Molecular Tools for Screening Biodiversity: Plants and Animals. Springer Dordrecht, pp. 59–63

    Chapter  Google Scholar 

  67. Kim C, Xi L, Cultraro CM, et al (2021) Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma. Cancers 13:3342. https://doi.org/10.3390/cancers13133342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kim H, Chung J-H (2015) Overview of clinicopathologic features of ALK-rearranged lung adenocarcinoma and current diagnostic testing for ALK rearrangement. Transl Lung Cancer Res 4:149–155. https://doi.org/10.3978/j.issn.2218-6751.2014.12.02

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kinde I, Wu J, Papadopoulos N, et al (2011) Detection and quantification of rare mutations with massively parallel sequencing. Proc Natl Acad Sci U S A 108:9530–9535. https://doi.org/10.1073/pnas.1105422108

    Article  PubMed  PubMed Central  Google Scholar 

  70. Kloten V, Rüchel N, Brüchle NO, et al (2017) Liquid biopsy in colon cancer: comparison of different circulating DNA extraction systems following absolute quantification of KRAS mutations using Intplex allele-specific PCR. Oncotarget 8:86253–86263. https://doi.org/10.18632/oncotarget.21134

    Article  PubMed  PubMed Central  Google Scholar 

  71. Kohler C, Radpour R, Barekati Z, et al (2009) Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors. Mol Cancer 8:105. https://doi.org/10.1186/1476-4598-8-105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kohno T, Ichikawa H, Totoki Y, et al (2012) KIF5B-RET fusions in lung adenocarcinoma. Nat Med 18:375–377. https://doi.org/10.1038/nm.2644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kris MG, Johnson BE, Berry LD, et al (2014) Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311:1998–2006. https://doi.org/10.1001/jama.2014.3741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kubo T, Yamamoto H, Lockwood WW, et al (2009) MET gene amplification or EGFR mutation activate MET in lung cancers untreated with EGFR tyrosine kinase inhibitors. Int J Cancer J Int Cancer 124:1778–1784. https://doi.org/10.1002/ijc.24150

    Article  CAS  Google Scholar 

  75. Kumar P, Dillon LW, Shibata Y, et al (2017) Normal and Cancerous Tissues Release Extrachromosomal Circular DNA (eccDNA) into the Circulation. Mol Cancer Res MCR 15:1197–1205. https://doi.org/10.1158/1541-7786.MCR-17-0095

    Article  CAS  PubMed  Google Scholar 

  76. Lanman RB, Mortimer SA, Zill OA, et al (2015) Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA. PloS One 10:e0140712. https://doi.org/10.1371/journal.pone.0140712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lennon AM, Buchanan AH, Kinde I, et al (2020) Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science 369. https://doi.org/10.1126/science.abb9601

  78. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ (1977) Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 37:646–650

    CAS  PubMed  Google Scholar 

  79. Li J, Wang L, Mamon H, et al (2008) Replacing PCR with COLD-PCR enriches variant DNA sequences and redefines the sensitivity of genetic testing. Nat Med 14:579–584. https://doi.org/10.1038/nm1708

    Article  CAS  PubMed  Google Scholar 

  80. Li N, Guha U, Kim C, et al (2020) Longitudinal Monitoring of EGFR and PIK3CA Mutations by Saliva-Based EFIRM in Advanced NSCLC Patients With Local Ablative Therapy and Osimertinib Treatment: Two Case Reports. Front Oncol 10. https://doi.org/10.3389/fonc.2020.01240

  81. Liang H, Liang W, Zhao L, et al (2018) Robotic Versus Video-assisted Lobectomy/Segmentectomy for Lung Cancer: A Meta-analysis. Ann Surg 268:254–259. https://doi.org/10.1097/SLA.0000000000002346

    Article  PubMed  Google Scholar 

  82. Lindeman NI, Cagle PT, Aisner DL, et al (2018) Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med 142:321–346. https://doi.org/10.5858/arpa.2017-0388-CP

    Article  CAS  PubMed  Google Scholar 

  83. Liu MC, Oxnard GR, Klein EA, et al (2020) Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol 31:745–759. https://doi.org/10.1016/j.annonc.2020.02.011

    Article  CAS  PubMed  Google Scholar 

  84. Lo YM, Corbetta N, Chamberlain PF, et al (1997) Presence of fetal DNA in maternal plasma and serum. Lancet Lond Engl 350:485–487. https://doi.org/10.1016/S0140-6736(97)02174-0

    Article  CAS  Google Scholar 

  85. Lui YYN, Chik K-W, Chiu RWK, et al (2002) Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation. Clin Chem 48:421–427

    Article  CAS  PubMed  Google Scholar 

  86. Luo J, Shen L, Zheng D (2014a) Diagnostic value of circulating free DNA for the detection of EGFR mutation status in NSCLC: a systematic review and meta-analysis. Sci Rep 4:6269. https://doi.org/10.1038/srep06269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Luo L, Zhang S, Wang Y, et al (2014b) Proinflammatory role of neutrophil extracellular traps in abdominal sepsis. Am J Physiol Lung Cell Mol Physiol 307:L586–596. https://doi.org/10.1152/ajplung.00365.2013

    Article  CAS  PubMed  Google Scholar 

  88. Ma L, Li H, Wang D, et al (2021) Dynamic cfDNA Analysis by NGS in EGFR T790M-Positive Advanced NSCLC Patients Failed to the First-Generation EGFR-TKIs. Front Oncol 11

    Google Scholar 

  89. Malapelle U, Sirera R, Jantus-Lewintre E, et al (2017) Profile of the Roche cobas® EGFR mutation test v2 for non-small cell lung cancer. Expert Rev Mol Diagn 17:209–215. https://doi.org/10.1080/14737159.2017.1288568

    Article  CAS  PubMed  Google Scholar 

  90. Mandel P, Metais, P (1948) Les acides nucléiques du plasma sanguin chez l’Homme. C R Seances Soc Biol Fil 241–243

    Google Scholar 

  91. McCoach CE, Le AT, Gowan K, et al (2018) Resistance Mechanisms to Targeted Therapies in ROS1+ and ALK+ Non-small Cell Lung Cancer. Clin Cancer Res Off J Am Assoc Cancer Res 24:3334–3347. https://doi.org/10.1158/1078-0432.CCR-17-2452

    Article  CAS  Google Scholar 

  92. Mok T, Wu Y-L, Lee JS, et al (2015) Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy. Clin Cancer Res 21:3196–3203. https://doi.org/10.1158/1078-0432.CCR-14-2594

    Article  CAS  PubMed  Google Scholar 

  93. Morozkin ES, Laktionov PP, Rykova EY, Vlassov VV (2004) Extracellular nucleic acids in cultures of long-term cultivated eukaryotic cells. Ann N Y Acad Sci 1022:244–249. https://doi.org/10.1196/annals.1318.038

    Article  CAS  PubMed  Google Scholar 

  94. Mouliere F, Chandrananda D, Piskorz AM, et al (2018) Enhanced detection of circulating tumor DNA by fragment size analysis. Sci Transl Med 10. https://doi.org/10.1126/scitranslmed.aat4921

  95. Napirei M, Ludwig S, Mezrhab J, et al (2009) Murine serum nucleases--contrasting effects of plasmin and heparin on the activities of DNase1 and DNase1-like 3 (DNase1l3). FEBS J 276:1059–1073. https://doi.org/10.1111/j.1742-4658.2008.06849.x

    Article  CAS  PubMed  Google Scholar 

  96. Newman AM, Bratman SV, To J, et al (2014) An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med 20:548–554. https://doi.org/10.1038/nm.3519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Newman AM, Lovejoy AF, Klass DM, et al (2016) Integrated digital error suppression for improved detection of circulating tumor DNA. Nat Biotechnol 34:547–555. https://doi.org/10.1038/nbt.3520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Newton CR, Graham A, Heptinstall LE, et al (1989) Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 17:2503–2516. https://doi.org/10.1093/nar/17.7.2503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Oruba A, Saccani S, van Essen D (2020) Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters. Nat Commun 11:1075. https://doi.org/10.1038/s41467-020-14950-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Pancer LB, Milazzo MF, Morris VL, et al (1981) Immunogenicity and characterization of supernatant DNA released by murine spleen cells. J Immunol Baltim Md 1950 127:98–104

    Google Scholar 

  101. Parikh AR, Van Seventer EE, Siravegna G, et al (2021) Minimal Residual Disease Detection using a Plasma-only Circulating Tumor DNA Assay in Patients with Colorectal Cancer. Clin Cancer Res Off J Am Assoc Cancer Res 27:5586–5594. https://doi.org/10.1158/1078-0432.CCR-21-0410

    Article  CAS  Google Scholar 

  102. Park C-K, Cho H-J, Choi Y-D, et al (2019) A Phase II Trial of Osimertinib in the Second-Line Treatment of Non-small Cell Lung Cancer with the EGFR T790M Mutation, Detected from Circulating Tumor DNA: LiquidLung-O-Cohort 2. Cancer Res Treat Off J Korean Cancer Assoc 51:777–787. https://doi.org/10.4143/crt.2018.387

    Article  CAS  Google Scholar 

  103. Pös O, Biró O, Szemes T, Nagy B (2018) Circulating cell-free nucleic acids: characteristics and applications. Eur J Hum Genet EJHG 26:937–945. https://doi.org/10.1038/s41431-018-0132-4

    Article  CAS  PubMed  Google Scholar 

  104. Pu D, Liang H, Wei F, et al (2016) Evaluation of a novel saliva-based epidermal growth factor receptor mutation detection for lung cancer: A pilot study. Thorac Cancer 7:428–436. https://doi.org/10.1111/1759-7714.12350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Qiu P, Poehlein CH, Marton MJ, et al (2019) Measuring Tumor Mutational Burden (TMB) in Plasma from mCRPC Patients Using Two Commercial NGS Assays. Sci Rep 9:114. https://doi.org/10.1038/s41598-018-37128-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Rainer TH, Wong LKS, Lam W, et al (2003) Prognostic use of circulating plasma nucleic acid concentrations in patients with acute stroke. Clin Chem 49:562–569. https://doi.org/10.1373/49.4.562

    Article  CAS  PubMed  Google Scholar 

  107. Raja R, Kuziora M, Brohawn PZ, et al (2018) Early Reduction in ctDNA Predicts Survival in Patients with Lung and Bladder Cancer Treated with Durvalumab. Clin Cancer Res Off J Am Assoc Cancer Res 24:6212–6222. https://doi.org/10.1158/1078-0432.CCR-18-0386

    Article  CAS  Google Scholar 

  108. Ramalingam SS, Vansteenkiste J, Planchard D, et al (2020) Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med 382:41–50. https://doi.org/10.1056/NEJMoa1913662

    Article  CAS  PubMed  Google Scholar 

  109. Razavi P, Li BT, Brown DN, et al (2019) High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants. Nat Med 25:1928–1937. https://doi.org/10.1038/s41591-019-0652-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Reinert T, Henriksen TV, Christensen E, et al (2019) Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA Oncol 5:1124–1131. https://doi.org/10.1001/jamaoncol.2019.0528

    Article  PubMed  PubMed Central  Google Scholar 

  111. Rizvi NA, Hellmann MD, Snyder A, et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128. https://doi.org/10.1126/science.aaa1348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Rolfo C, Mack PC, Scagliotti GV, et al (2018) Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 13:1248–1268. https://doi.org/10.1016/j.jtho.2018.05.030

    Article  Google Scholar 

  113. Rosell R, Carcereny E, Gervais R, et al (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13:239–246. https://doi.org/10.1016/S1470-2045(11)70393-X

    Article  CAS  PubMed  Google Scholar 

  114. Rostami A, Lambie M, Yu CW, et al (2020) Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics. Cell Rep 31:107830. https://doi.org/10.1016/j.celrep.2020.107830

    Article  CAS  PubMed  Google Scholar 

  115. Roviello G, D’Angelo A, Sirico M, et al (2021) Advances in anti-BRAF therapies for lung cancer. Invest New Drugs 39:879–890. https://doi.org/10.1007/s10637-021-01068-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Rowlands V, Rutkowski AJ, Meuser E, et al (2019) Optimisation of robust singleplex and multiplex droplet digital PCR assays for high confidence mutation detection in circulating tumour DNA. Sci Rep 9:12620. https://doi.org/10.1038/s41598-019-49043-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Rykova EY, Morozkin ES, Ponomaryova AA, et al (2012) Cell-free and cell-bound circulating nucleic acid complexes: mechanisms of generation, concentration and content. Expert Opin Biol Ther 12 Suppl 1:S141–153. https://doi.org/10.1517/14712598.2012.673577

    Article  CAS  PubMed  Google Scholar 

  118. Rykova EYu Null, Pautova LV, Yakubov LA, et al (1994) Serum immunoglobulins interact with oligonucleotides. FEBS Lett 344:96–98. https://doi.org/10.1016/0014-5793(94)00360-2

    Article  CAS  PubMed  Google Scholar 

  119. Sacher AG, Komatsubara KM, Oxnard GR (2017) Application of Plasma Genotyping Technologies in Non-Small Cell Lung Cancer: A Practical Review. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 12:1344–1356. https://doi.org/10.1016/j.jtho.2017.05.022

    Article  Google Scholar 

  120. Sacher AG, Paweletz C, Dahlberg SE, et al (2016) Prospective Validation of Rapid Plasma Genotyping for the Detection of EGFR and KRAS Mutations in Advanced Lung Cancer. JAMA Oncol 2:1014–1022. https://doi.org/10.1001/jamaoncol.2016.0173

    Article  PubMed  PubMed Central  Google Scholar 

  121. Sanchez C, Roch B, Mazard T, et al (2021) Circulating nuclear DNA structural features, origins, and complete size profile revealed by fragmentomics. JCI Insight 6:144561. https://doi.org/10.1172/jci.insight.144561

    Article  PubMed  Google Scholar 

  122. Schmitt MW, Kennedy SR, Salk JJ, et al (2012) Detection of ultra-rare mutations by next-generation sequencing. Proc Natl Acad Sci U S A 109:14508–14513. https://doi.org/10.1073/pnas.1208715109

    Article  PubMed  PubMed Central  Google Scholar 

  123. Shen SY, Singhania R, Fehringer G, et al (2018) Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature 563:579–583. https://doi.org/10.1038/s41586-018-0703-0

    Article  CAS  PubMed  Google Scholar 

  124. Smith ZD, Meissner A (2013) DNA methylation: roles in mammalian development. Nat Rev Genet 14:204–220. https://doi.org/10.1038/nrg3354

    Article  CAS  PubMed  Google Scholar 

  125. Snyder MW, Kircher M, Hill AJ, et al (2016) Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin. Cell 164:57–68. https://doi.org/10.1016/j.cell.2015.11.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Sorensen BS, Wu L, Wei W, et al (2014) Monitoring of epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and resistance mutations in the plasma DNA of patients with advanced non-small cell lung cancer during treatment with erlotinib. Cancer 120:3896–3901. https://doi.org/10.1002/cncr.28964

    Article  CAS  PubMed  Google Scholar 

  127. Soria J-C, Ohe Y, Vansteenkiste J, et al (2018) Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med 378:113–125. https://doi.org/10.1056/NEJMoa1713137

    Article  CAS  PubMed  Google Scholar 

  128. Stroun M, Anker P, Maurice P, et al (1989) Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology 46:318–322. https://doi.org/10.1159/000226740

    Article  CAS  PubMed  Google Scholar 

  129. Sundaresan TK, Sequist LV, Heymach JV, et al (2016) Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses. Clin Cancer Res Off J Am Assoc Cancer Res 22:1103–1110. https://doi.org/10.1158/1078-0432.CCR-15-1031

    Article  CAS  Google Scholar 

  130. Suzuki MM, Bird A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9:465–476. https://doi.org/10.1038/nrg2341

    Article  CAS  PubMed  Google Scholar 

  131. Tetta C, Ghigo E, Silengo L, et al (2013) Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine 44:11–19. https://doi.org/10.1007/s12020-012-9839-0

    Article  CAS  PubMed  Google Scholar 

  132. Thakur BK, Zhang H, Becker A, et al (2014) Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res 24:766–769. https://doi.org/10.1038/cr.2014.44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Travis WD, Brambilla E, Nicholson AG, et al (2015) The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 10:1243–1260. https://doi.org/10.1097/JTO.0000000000000630

    Article  Google Scholar 

  134. Troll CJ, Kapp J, Rao V, et al (2019) A ligation-based single-stranded library preparation method to analyze cell-free DNA and synthetic oligos. BMC Genomics 20:1023. https://doi.org/10.1186/s12864-019-6355-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Tu M, Cheng J, Chen Y-L, et al (2020) Electric Field-Induced Release and Measurement (EFIRM): Characterization and Technical Validation of a Novel Liquid Biopsy Platform in Plasma and Saliva. J Mol Diagn JMD 22:1050–1062. https://doi.org/10.1016/j.jmoldx.2020.05.005

    Article  CAS  PubMed  Google Scholar 

  136. van der Leest P, Boonstra PA, ter Elst A, et al (2020) Comparison of Circulating Cell-Free DNA Extraction Methods for Downstream Analysis in Cancer Patients. Cancers 12. https://doi.org/10.3390/cancers12051222

  137. Vasioukhin V, Anker P, Maurice P, et al (1994) Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br J Haematol 86:774–779. https://doi.org/10.1111/j.1365-2141.1994.tb04828.x

    Article  CAS  PubMed  Google Scholar 

  138. Wan Y, Cheng G, Liu X, et al (2017) Rapid magnetic isolation of extracellular vesicles via lipid-based nanoprobes. Nat Biomed Eng 1. https://doi.org/10.1038/s41551-017-0058

  139. Wang L, Xie L, Zhang Q, et al (2015) Plasma nuclear and mitochondrial DNA levels in acute myocardial infarction patients. Coron Artery Dis 26:296–300. https://doi.org/10.1097/MCA.0000000000000231

    Article  PubMed  PubMed Central  Google Scholar 

  140. Wang Z, Cheng Y, An T, et al (2018) Detection of EGFR mutations in plasma circulating tumour DNA as a selection criterion for first-line gefitinib treatment in patients with advanced lung adenocarcinoma (BENEFIT): a phase 2, single-arm, multicentre clinical trial. Lancet Respir Med 6:681–690. https://doi.org/10.1016/S2213-2600(18)30264-9

    Article  CAS  PubMed  Google Scholar 

  141. Wang Z, Duan J, Cai S, et al (2019) Assessment of Blood Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Patients With Non–Small Cell Lung Cancer With Use of a Next-Generation Sequencing Cancer Gene Panel. JAMA Oncol 5:696–702. https://doi.org/10.1001/jamaoncol.2018.7098

    Article  PubMed  PubMed Central  Google Scholar 

  142. Wei F, Strom CM, Cheng J, et al (2018) Electric Field-Induced Release and Measurement Liquid Biopsy for Noninvasive Early Lung Cancer Assessment. J Mol Diagn JMD. https://doi.org/10.1016/j.jmoldx.2018.06.008

  143. Wei F, Yang J, Wong DTW (2013) Detection of exosomal biomarker by electric field-induced release and measurement (EFIRM). Biosens Bioelectron 44:115–121. https://doi.org/10.1016/j.bios.2012.12.046

    Article  CAS  PubMed  Google Scholar 

  144. Wu LR, Chen SX, Wu Y, et al (2017) Multiplexed enrichment of rare DNA variants via sequence-selective and temperature-robust amplification. Nat Biomed Eng 1:714–723. https://doi.org/10.1038/s41551-017-0126-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Xavier CPR, Caires HR, Barbosa MAG, et al (2020) The Role of Extracellular Vesicles in the Hallmarks of Cancer and Drug Resistance. Cells 9. https://doi.org/10.3390/cells9051141

  146. Yan Y, Guo G, Huang J, et al (2020) Current understanding of extrachromosomal circular DNA in cancer pathogenesis and therapeutic resistance. J Hematol OncolJ Hematol Oncol 13:124. https://doi.org/10.1186/s13045-020-00960-9

    Article  CAS  Google Scholar 

  147. Yang X, Cai G-X, Han B-W, et al (2021) Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer. Npj Breast Cancer 7:1–12. https://doi.org/10.1038/s41523-021-00237-5

    Article  CAS  Google Scholar 

  148. Yousefi S, Gold JA, Andina N, et al (2008) Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat Med 14:949–953. https://doi.org/10.1038/nm.1855

    Article  CAS  PubMed  Google Scholar 

  149. Zhang R, Nakahira K, Guo X, et al (2016) Very Short Mitochondrial DNA Fragments and Heteroplasmy in Human Plasma. Sci Rep 6:36097. https://doi.org/10.1038/srep36097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Zheng D, Ye X, Zhang MZ, et al (2016) Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance. Sci Rep 6:20913. https://doi.org/10.1038/srep20913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Zhou Z, Cheng SH, Ding SC, et al (2021) Jagged Ends of Urinary Cell-Free DNA: Characterization and Feasibility Assessment in Bladder Cancer Detection. Clin Chem 67:621–630. https://doi.org/10.1093/clinchem/hvaa325

    Article  PubMed  Google Scholar 

  152. Zviran A, Schulman RC, Shah M, et al (2020) Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring. Nat Med 26:1114–1124. https://doi.org/10.1038/s41591-020-0915-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by grants (U01 CA233370; UH2/UH3 CA206126; R21 CA239052) from the National Institutes of Health (NIH) to D.T.W.W. The work was also supported by grants to A.A.P. from the NIH (U01 CA233364; R01 CA197486), the Yale SPORE in Lung Cancer (P50 CA196530), the Yale Cancer Center (P30 CA016359), and the Honorable Tina Brozman Foundation.

Additional funding sources include the Canadian Institute of Health Research Doctoral Foreign Study Award, Tobacco-Related Disease Research Program (TRDRP) Predoctoral Fellowship, Jonsson Comprehensive Cancer Center Predoctoral Fellowship, NIH grant UL1TR001881, and NCI F99CA26498-01 (JC).

Disclosures

Abhijit Patel

Stock and Other Ownership Interests: Binary Genomics (co-founder)

Honoraria: NuGEN

Consulting or Advisory Role: NuGEN, NuProbe USA, Kohlberg Kravis Roberts & Co., Inc.

Research Funding: AstraZeneca

Patents, Royalties, Other Intellectual Property: Inventor and assignee of patents and patent applications covering nucleic acid analysis technologies

Travel, Accommodations, Expenses: NuGEN, Statum Fund

David Wong

Stock and ownership interests: RNAmeTRIX LLC and Liquid Diagnostics

Consulting for: Colgate-Palmolive

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Authors and Affiliations

  1. Center for Oral/Head and Neck Oncology Research, School of Dentistry, University of California, Los Angeles, CA, USA

    Jordan Cheng & David T. W. Wong

  2. Department of Therapeutic Radiology, Yale School of Medicine, Yale University, New Haven, CT, USA

    Yiduo Hu & Abhijit A. Patel

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  1. Jordan Cheng
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Correspondence to Yiduo Hu or David T. W. Wong .

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Editors and Affiliations

  1. Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA

    Richard J. Cote

  2. ACTC Lab, Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece

    Evi Lianidou

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Cheng, J., Hu, Y., Wong, D.T.W., Patel, A.A. (2023). ctDNA and Lung Cancer. In: Cote, R.J., Lianidou, E. (eds) Circulating Tumor Cells. Current Cancer Research. Springer, Cham. https://doi.org/10.1007/978-3-031-22903-9_20

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