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Semin Thromb Hemost 2018; 44(02): 135-141
DOI: 10.1055/s-0037-1606182
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Platelet RNA in Cancer Diagnostics

Lee-Ann Tjon-Kon-Fat
1   Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden
,
Nik Sol
2   Cancer Center Amsterdam, Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands
,
Thomas Wurdinger
3   Cancer Center Amsterdam, Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands
4   Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, Massachusetts
,
R. Jonas A. Nilsson
1   Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden
› Author Affiliations
Further Information

Publication History

Publication Date:
13 September 2017 (online)

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Abstract

Platelets are involved in several steps of cancer metastasis. During this process, platelets are exposed to the tumor and its environment, thereby exchanging biomolecules with the tumor cells and resulting in tumor-mediated “education” of the platelets and a change in their RNA profile. Analysis of platelet RNA profiles or direct measurement of tumor-derived biomarkers within platelets can provide information on ongoing cancer-related processes in the individual (e.g., whether the patient has cancer, the tumor type, and possibly identify oncogenic alterations driving the disease for treatment selection). The close interaction with the disease process and the ability to respond to systemic alterations make platelets an interesting biosource for implementation in precision medicine.

Keywords

platelets - biomarkers - liquid biopsy
 

  • References

  • 1 Junt T, Schulze H, Chen Z. , et al. Dynamic visualization of thrombopoiesis within bone marrow. Science 2007; 317 (5845): 1767-1770
    CrossrefPubMedGoogle Scholar
  • 2 Schwertz H, Köster S, Kahr WH. , et al. Anucleate platelets generate progeny. Blood 2010; 115 (18) 3801-3809
    CrossrefPubMedGoogle Scholar
  • 3 Kaufman RM, Airo R, Pollack S, Crosby WH, Doberneck R. Origin of Pulmonary Megakaryocytes. Blood 1965; 25: 767-775
    CrossrefPubMedGoogle Scholar
  • 4 Lefrançais E, Ortiz-Muñoz G, Caudrillier A. , et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature 2017; 544 (7648): 105-109
    CrossrefPubMedGoogle Scholar
  • 5 Harker LA. The kinetics of platelet production and destruction in man. Clin Haematol 1977; 6 (03) 671-693
    PubMedGoogle Scholar
  • 6 Coller BS. Foreword: a brief history of ideas about platelets in health and disease. Platelets. 3rd ed. 2013: xix-xliv
    Google Scholar
  • 7 Wang Y, Andrews M, Yang Y. , et al. Platelets in thrombosis and hemostasis: old topic with new mechanisms. Cardiovasc Hematol Disord Drug Targets 2012; 12 (02) 126-132
    CrossrefPubMedGoogle Scholar
  • 8 Li C, Li J, Li Y. , et al. Crosstalk between platelets and the immune system: old systems with new discoveries. Adv Hematol 2012; 2012: 384685
    PubMedGoogle Scholar
  • 9 Semple JW, Italiano Jr JE, Freedman J. Platelets and the immune continuum. Nat Rev Immunol 2011; 11 (04) 264-274
    CrossrefPubMedGoogle Scholar
  • 10 Siegel-Axel D, Daub K, Seizer P, Lindemann S, Gawaz M. Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis. Cardiovasc Res 2008; 78 (01) 8-17
    CrossrefPubMedGoogle Scholar
  • 11 Murphy AJ, Bijl N, Yvan-Charvet L. , et al. Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis. Nat Med 2013; 19 (05) 586-594
    CrossrefPubMedGoogle Scholar
  • 12 Lindemann S, Krämer B, Seizer P, Gawaz M. Platelets, inflammation and atherosclerosis. J Thromb Haemost 2007; 5 (Suppl. 01) 203-211
    CrossrefPubMedGoogle Scholar
  • 13 Yougbaré I, Lang S, Yang H. , et al. Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage. J Clin Invest 2015; 125 (04) 1545-1556
    CrossrefPubMedGoogle Scholar
  • 14 Italiano Jr JE, Richardson JL, Patel-Hett S. , et al. Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood 2008; 111 (03) 1227-1233
    CrossrefPubMedGoogle Scholar
  • 15 Chatterjee M, Huang Z, Zhang W. , et al. Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli. Blood 2011; 117 (14) 3907-3911
    CrossrefPubMedGoogle Scholar
  • 16 Leslie M. Cell biology. Beyond clotting: the powers of platelets. Science 2010; 328 (5978): 562-564
    CrossrefPubMedGoogle Scholar
  • 17 Labelle M, Hynes RO. The initial hours of metastasis: the importance of cooperative host-tumor cell interactions during hematogenous dissemination. Cancer Discov 2012; 2 (12) 1091-1099
    CrossrefPubMedGoogle Scholar
  • 18 Labelle M, Begum S, Hynes RO. Platelets guide the formation of early metastatic niches. Proc Natl Acad Sci U S A 2014; 111 (30) E3053-E3061
    CrossrefPubMedGoogle Scholar
  • 19 Franco AT, Corken A, Ware J. Platelets at the interface of thrombosis, inflammation, and cancer. Blood 2015; 126 (05) 582-588
    CrossrefPubMedGoogle Scholar
  • 20 White JG. Platelets are covercytes, not phagocytes: uptake of bacteria involves channels of the open canalicular system. Platelets 2005; 16 (02) 121-131
    CrossrefPubMedGoogle Scholar
  • 21 Lee TH, Stromberg RR, Henrard D, Busch MP. Effect of platelet-associated virus on assays of HIV-1 in plasma. Science 1993; 262 (5139): 1585-1586
    PubMedGoogle Scholar
  • 22 Youssefian T, Drouin A, Massé JM, Guichard J, Cramer EM. Host defense role of platelets: engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Blood 2002; 99 (11) 4021-4029
    CrossrefPubMedGoogle Scholar
  • 23 Lee TH, Stromberg RR, Heitman JW, Sawyer L, Hanson CV, Busch MP. Distribution of HIV type 1 (HIV-1) in blood components: detection and significance of high levels of HIV-1 associated with platelets. Transfusion 1998; 38 (06) 580-588
    CrossrefPubMedGoogle Scholar
  • 24 Verheul HM, Lolkema MP, Qian DZ. , et al. Platelets take up the monoclonal antibody bevacizumab. Clin Cancer Res 2007; 13 (18 Pt 1): 5341-5347
    CrossrefPubMedGoogle Scholar
  • 25 Klement GL, Yip TT, Cassiola F. , et al. Platelets actively sequester angiogenesis regulators. Blood 2009; 113 (12) 2835-2842
    CrossrefPubMedGoogle Scholar
  • 26 Nilsson RJ, Balaj L, Hulleman E. , et al. Blood platelets contain tumor-derived RNA biomarkers. Blood 2011; 118 (13) 3680-3683
    CrossrefPubMedGoogle Scholar
  • 27 Clancy L, Beaulieu LM, Tanriverdi K, Freedman JE. The role of RNA uptake in platelet heterogeneity. Thromb Haemost 2017; 117 (05) 948-961
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Levin J. The evolution of mammalian platelets. Platelets. 3rd ed. 2013: 3-26
    Google Scholar
  • 29 Mercado CP, Kilic F. Molecular mechanisms of SERT in platelets: regulation of plasma serotonin levels. Mol Interv 2010; 10 (04) 231-241
    CrossrefPubMedGoogle Scholar
  • 30 Lopez-Vilchez I, Diaz-Ricart M, Galan AM. , et al. Internalization of tissue factor-rich microvesicles by platelets occurs independently of GPIIb-IIIa, and involves cd36 receptor, serotonin transporter and cytoskeletal assembly. J Cell Biochem 2016; 117 (02) 448-457
    CrossrefPubMedGoogle Scholar
  • 31 Escolar G, Lopez-Vilchez I, Diaz-Ricart M, White JG, Galan AM. Internalization of tissue factor by platelets. Thromb Res 2008; 122 (Suppl. 01) S37-S41
    CrossrefPubMedGoogle Scholar
  • 32 Behnke O. Electron microscopic observations on the membrane systems of the rat blood platelet. Anat Rec 1967; 158 (02) 121-137
    CrossrefPubMedGoogle Scholar
  • 33 Chapman LM, Aggrey AA, Field DJ. , et al. Platelets present antigen in the context of MHC class I. J Immunol 2012; 189 (02) 916-923
    CrossrefPubMedGoogle Scholar
  • 34 Placke T, Örgel M, Schaller M. , et al. Platelet-derived MHC class I confers a pseudonormal phenotype to cancer cells that subverts the antitumor reactivity of natural killer immune cells. Cancer Res 2012; 72 (02) 440-448
    CrossrefPubMedGoogle Scholar
  • 35 Bailey SE, Ukoumunne OC, Shephard EA, Hamilton W. Clinical relevance of thrombocytosis in primary care: a prospective cohort study of cancer incidence using English electronic medical records and cancer registry data. Br J Gen Pract 2017; 67 (659) e405-e413
    CrossrefPubMedGoogle Scholar
  • 36 Stone RL, Nick AM, McNeish IA. , et al. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med 2012; 366 (07) 610-618
    CrossrefPubMedGoogle Scholar
  • 37 Ferroni P, Riondino S, Formica V. , et al. Venous thromboembolism risk prediction in ambulatory cancer patients: clinical significance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio. Int J Cancer 2015; 136 (05) 1234-1240
    CrossrefPubMedGoogle Scholar
  • 38 Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet 2012; 379 (9826): 1591-1601
    CrossrefPubMedGoogle Scholar
  • 39 Wang R, Stone RL, Kaelber JT. , et al. Electron cryotomography reveals ultrastructure alterations in platelets from patients with ovarian cancer. Proc Natl Acad Sci U S A 2015; 112 (46) 14266-14271
    CrossrefPubMedGoogle Scholar
  • 40 McAllister SS, Weinberg RA. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol 2014; 16 (08) 717-727
    CrossrefPubMedGoogle Scholar
  • 41 Stegner D, Dütting S, Nieswandt B. Mechanistic explanation for platelet contribution to cancer metastasis. Thromb Res 2014; 133 (Suppl. 02) S149-S157
    CrossrefPubMedGoogle Scholar
  • 42 Tesfamariam B. Involvement of platelets in tumor cell metastasis. Pharmacol Ther 2016; 157: 112-119
    CrossrefPubMedGoogle Scholar
  • 43 Gasic GJ, Gasic TB, Stewart CC. Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci U S A 1968; 61 (01) 46-52
    CrossrefPubMedGoogle Scholar
  • 44 Buergy D, Wenz F, Groden C, Brockmann MA. Tumor-platelet interaction in solid tumors. Int J Cancer 2012; 130 (12) 2747-2760
    CrossrefPubMedGoogle Scholar
  • 45 Jia Y, Zhang S, Miao L. , et al. Activation of platelet protease-activated receptor-1 induces epithelial-mesenchymal transition and chemotaxis of colon cancer cell line SW620. Oncol Rep 2015; 33 (06) 2681-2688
    CrossrefPubMedGoogle Scholar
  • 46 Kong D, Wang Z, Sarkar SH. , et al. Platelet-derived growth factor-D overexpression contributes to epithelial-mesenchymal transition of PC3 prostate cancer cells. Stem Cells 2008; 26 (06) 1425-1435
    CrossrefPubMedGoogle Scholar
  • 47 Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139 (05) 871-890
    CrossrefPubMedGoogle Scholar
  • 48 Miyashita T, Tajima H, Makino I. , et al. Metastasis-promoting role of extravasated platelet activation in tumor. J Surg Res 2015; 193 (01) 289-294
    CrossrefPubMedGoogle Scholar
  • 49 Rolli M, Fransvea E, Pilch J, Saven A, Felding-Habermann B. Activated integrin alphavbeta3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells. Proc Natl Acad Sci U S A 2003; 100 (16) 9482-9487
    CrossrefPubMedGoogle Scholar
  • 50 Chen YQ, Liu B, Tang DG, Honn KV. Fatty acid modulation of tumor cell-platelet-vessel wall interaction. Cancer Metastasis Rev 1992; 11 (3-4): 389-409
    CrossrefPubMedGoogle Scholar
  • 51 Medina VA, Rivera ES. Histamine receptors and cancer pharmacology. Br J Pharmacol 2010; 161 (04) 755-767
    CrossrefPubMedGoogle Scholar
  • 52 Skolnik G, Bagge U, Blomqvist G, Djärv L, Ahlman H. The role of calcium channels and serotonin (5-HT2) receptors for tumour cell lodgement in the liver. Clin Exp Metastasis 1989; 7 (02) 169-174
    CrossrefPubMedGoogle Scholar
  • 53 Menter DG, Hatfield JS, Harkins C. , et al. Tumor cell-platelet interactions in vitro and their relationship to in vivo arrest of hematogenously circulating tumor cells. Clin Exp Metastasis 1987; 5 (01) 65-78
    CrossrefPubMedGoogle Scholar
  • 54 Chen M, Geng JG. P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis. Arch Immunol Ther Exp (Warsz) 2006; 54 (02) 75-84
    CrossrefPubMedGoogle Scholar
  • 55 Palumbo JS, Talmage KE, Massari JV. , et al. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 2005; 105 (01) 178-185
    CrossrefPubMedGoogle Scholar
  • 56 Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer 2011; 11 (02) 123-134
    CrossrefPubMedGoogle Scholar
  • 57 Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci U S A 2001; 98 (06) 3352-3357
    CrossrefPubMedGoogle Scholar
  • 58 Kopp HG, Placke T, Salih HR. Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res 2009; 69 (19) 7775-7783
    CrossrefPubMedGoogle Scholar
  • 59 Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 2011; 20 (05) 576-590
    CrossrefPubMedGoogle Scholar
  • 60 Schumacher D, Strilic B, Sivaraj KK, Wettschureck N, Offermanns S. Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell 2013; 24 (01) 130-137
    CrossrefPubMedGoogle Scholar
  • 61 McCarty OJ, Mousa SA, Bray PF, Konstantopoulos K. Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions. Blood 2000; 96 (05) 1789-1797
    CrossrefPubMedGoogle Scholar
  • 62 Kerr BA, McCabe NP, Feng W, Byzova TV. Platelets govern pre-metastatic tumor communication to bone. Oncogene 2013; 32 (36) 4319-4324
    CrossrefPubMedGoogle Scholar
  • 63 Erpenbeck L, Schön MP. Deadly allies: the fatal interplay between platelets and metastasizing cancer cells. Blood 2010; 115 (17) 3427-3436
    CrossrefPubMedGoogle Scholar
  • 64 Malik AB. Pulmonary microembolism. Physiol Rev 1983; 63 (03) 1114-1207
    CrossrefPubMedGoogle Scholar
  • 65 Verheul HM, Jorna AS, Hoekman K, Broxterman HJ, Gebbink MF, Pinedo HM. Vascular endothelial growth factor-stimulated endothelial cells promote adhesion and activation of platelets. Blood 2000; 96 (13) 4216-4221
    Google Scholar
  • 66 Boucharaba A, Serre CM, Grès S. , et al. Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J Clin Invest 2004; 114 (12) 1714-1725
    CrossrefPubMedGoogle Scholar
  • 67 Honn KV, Tang DG, Chen YQ. Platelets and cancer metastasis: more than an epiphenomenon. Semin Thromb Hemost 1992; 18 (04) 392-415
    Article in Thieme ConnectPubMedGoogle Scholar
  • 68 Kuznetsov HS, Marsh T, Markens BA. , et al. Identification of luminal breast cancers that establish a tumor-supportive macroenvironment defined by proangiogenic platelets and bone marrow-derived cells. Cancer Discov 2012; 2 (12) 1150-1165
    CrossrefPubMedGoogle Scholar
  • 69 Peterson JE, Zurakowski D, Italiano Jr JE. , et al. Normal ranges of angiogenesis regulatory proteins in human platelets. Am J Hematol 2010; 85 (07) 487-493
    CrossrefPubMedGoogle Scholar
  • 70 Brill A, Dashevsky O, Rivo J, Gozal Y, Varon D. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res 2005; 67 (01) 30-38
    CrossrefPubMedGoogle Scholar
  • 71 Kisucka J, Butterfield CE, Duda DG. , et al. Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage. Proc Natl Acad Sci U S A 2006; 103 (04) 855-860
    CrossrefPubMedGoogle Scholar
  • 72 Chiodoni C, Iezzi M, Guiducci C. , et al. Triggering CD40 on endothelial cells contributes to tumor growth. J Exp Med 2006; 203 (11) 2441-2450
    CrossrefPubMedGoogle Scholar
  • 73 Ho-Tin-Noé B, Goerge T, Cifuni SM, Duerschmied D, Wagner DD. Platelet granule secretion continuously prevents intratumor hemorrhage. Cancer Res 2008; 68 (16) 6851-6858
    CrossrefPubMedGoogle Scholar
  • 74 Nilsson RJ, Karachaliou N, Berenguer J. , et al. Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer. Oncotarget 2016; 7 (01) 1066-1075
    PubMedGoogle Scholar
  • 75 Corduan A, Plé H, Laffont B. , et al. Dissociation of SERPINE1 mRNA from the translational repressor proteins Ago2 and TIA-1 upon platelet activation. Thromb Haemost 2015; 113 (05) 1046-1059
    Article in Thieme ConnectPubMedGoogle Scholar
  • 76 Denis MM, Tolley ND, Bunting M. , et al. Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. Cell 2005; 122 (03) 379-391
    CrossrefPubMedGoogle Scholar
  • 77 Alhasan AA, Izuogu OG, Al-Balool HH. , et al. Circular RNA enrichment in platelets is a signature of transcriptome degradation. Blood 2016; 127 (09) e1-e11
    CrossrefPubMedGoogle Scholar
  • 78 Guarnerio J, Bezzi M, Jeong JC. , et al. Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell 2016; 166 (04) 1055-1056
    PubMedGoogle Scholar
  • 79 Risitano A, Beaulieu LM, Vitseva O, Freedman JE. Platelets and platelet-like particles mediate intercellular RNA transfer. Blood 2012; 119 (26) 6288-6295
    CrossrefPubMedGoogle Scholar
  • 80 Laffont B, Corduan A, Rousseau M. , et al. Platelet microparticles reprogram macrophage gene expression and function. Thromb Haemost 2016; 115 (02) 311-323
    Article in Thieme ConnectPubMedGoogle Scholar
  • 81 Angénieux C, Maître B, Eckly A, Lanza F, Gachet C, de la Salle H. Time-dependent decay of mRNA and ribosomal RNA during platelet aging and its correlation with translation activity. PLoS One 2016; 11 (01) e0148064
    CrossrefPubMedGoogle Scholar
  • 82 Salvagno GL, Montagnana M, Degan M. , et al. Evaluation of platelet turnover by flow cytometry. Platelets 2006; 17 (03) 170-177
    CrossrefPubMedGoogle Scholar
  • 83 Shashkin PN, Brown GT, Ghosh A, Marathe GK, McIntyre TM. Lipopolysaccharide is a direct agonist for platelet RNA splicing. J Immunol 2008; 181 (05) 3495-3502
    CrossrefPubMedGoogle Scholar
  • 84 Schwertz H, Tolley ND, Foulks JM. , et al. Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenicity of human platelets. J Exp Med 2006; 203 (11) 2433-2440
    CrossrefPubMedGoogle Scholar
  • 85 Best MG, Sol N, Kooi I. , et al. RNA-seq of tumor-educated platelets enables blood-based pan-cancer, multiclass, and molecular pathway cancer diagnostics. Cancer Cell 2015; 28 (05) 666-676
    CrossrefPubMedGoogle Scholar
  • 86 Best MG. Tumor-educated platelets as a blood-based liquid biopsy platform for cancer diagnostics. In: 24th International Molecular Medicine Tri-Conference; February 20–22, 2017; San Francisco, CA
    PubMedGoogle Scholar
  • 87 Jahr S, Hentze H, Englisch S. , et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 2001; 61 (04) 1659-1665
    PubMedGoogle Scholar
  • 88 Capel B, Swain A, Nicolis S. , et al. Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell 1993; 73 (05) 1019-1030
    CrossrefPubMedGoogle Scholar
  • 89 Chan AT, Ogino S, Fuchs CS. Aspirin use and survival after diagnosis of colorectal cancer. JAMA 2009; 302 (06) 649-658
    CrossrefPubMedGoogle Scholar
  • 90 Guo S, Diep D, Plongthongkum N, Fung HL, Zhang K, Zhang K. Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA. Nat Genet 2017; 49 (04) 635-642
    CrossrefPubMedGoogle Scholar
  • 91 Gormally E, Vineis P, Matullo G. , et al. TP53 and KRAS2 mutations in plasma DNA of healthy subjects and subsequent cancer occurrence: a prospective study. Cancer Res 2006; 66 (13) 6871-6876
    CrossrefPubMedGoogle Scholar
  • 92 Holstege H, Pfeiffer W, Sie D. , et al. Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis. Genome Res 2014; 24 (05) 733-742
    CrossrefPubMedGoogle Scholar
  • 93 Pedram R, Li BT, Hou C. , et al. Cell-free DNA (cfDNA) mutations from clonal hematopoiesis: Implications for interpretation of liquid biopsy tests. J Clin Oncol 2017; 35 (suppl): abstr 11526
    PubMedGoogle Scholar
  • 94 Morrison C. Search for liquid biopsy grail points the way to drug discovery and development gems. Nat Rev Drug Discov 2017; 16 (06) 373-374
    CrossrefPubMedGoogle Scholar
  • 95 Aravanis AM, Lee M, Klausner RD. Next-Generation Sequencing of Circulating Tumor DNA for Early Cancer Detection. Cell 2017; 168 (04) 571-574
    CrossrefPubMedGoogle Scholar