Potential of Cell‑free Circulating DNA in Diagnosis of Cancer
Authors:
V. Kubaczkova 1,2; L. Sedlaříková 1,2; L. Bešše 1; M. Almaši 1,2; Hájek R. 1–3; S. Ševčíková 1,2
Authors‘ workplace:
Babákova myelomová skupina, Ústav patologické fyziologie, LF MU, Brno
1; Oddělení klinické hematologie, FN Brno
2; Klinika hematoonkologie LF OU a FN Ostrava
3
Published in:
Klin Onkol 2015; 28(4): 251-259
Category:
Review
doi:
https://doi.org/10.14735/amko2015251
Overview
Circulating cell‑free DNA (cf‑DNA) is characterized as extracellular DNA that may be present in the blood of healthy individuals in low concentrations. Cf‑DNA is released by apoptosis or necrosis into the bloodstream. Increased levels are found in pathological conditions, such as inflammation, autoimmune diseases, or stress. Significant increase of cf‑DNA is particularly evident in patients with malignancies, especially in the advanced stages of the disease. In this case, the tumor specific cf‑DNA is released by necrosis from the cells of primary tumor and metastases. Recently, many studies concentrate on the so‑ called ‘liquid biopsies’ that allow detection of circulating tumor cells and circulating nucleic acids from peripheral blood for tumor diagnostics. Quantitative methods and detection of genetic and epigenetic alternations of cf‑DNA in patients with different malignancies have potential applications in molecular diagnosis, prognosis, monitoring of disease progression and response to treatment. This review focuses on potential utility of cf‑DNA as a blood biomarker in selected solid tumors and hematologic malignancies.
Key words:
circulating cell‑free DNA – tumor marker – solid tumors – hematological malignancies
This study was supported by grant of Internal Grant Agency of the Czech Ministry of Health NT14575.
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
Submitted:
13. 3. 2015
Accepted:
18. 5. 2015
Sources
1. 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(4): 1659– 1665.
2. Mandel P, Metais P. Les acides nucleiques du plasma sanguin chezl‘homme. C R Seances Soc Biol Fil 1948; 142(3– 4): 241– 243.
3. Leon SA, Shapiro B, Sklaroff DM et al. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 1977; 37(3): 646– 650.
4. Anker P, Stroun M. Circulating DNA in plasma or serum, Medicina (B Aires) 2000; 60(5 Pt 2): 699– 702.
5. Stroun M, Lyautey J, Lederrey C et al. About the possible origin and mechanism of circulating DNA: apoptosis and active DNA release. Clin Chim Acta 2001; 313(1– 2): 139– 142.
6. Zeerleder S. The struggle to detect circulating DNA. Crit Care 2006; 10(3): 142.
7. Rumore PM, Steinman CR. Endogenous circulating DNA in systemic lupus erythematosus. Occurrence as multimeric complexes bound to histone. J Clin Invest 1990; 86(1): 69– 74.
8. Zeerleder S, Zwart B, Wuillemin WA et al. Elevated nucleosome levels in systemic inflammation and sepsis. Crit Care Med 2003; 31(7): 1947– 5191.
9. Lo YMD, Rainer TH, Chan LYS et al. Plasma DNA as a prognostic marker in trauma patients. Clin Chem 2000; 46(3): 319– 323.
10. Rainer TH, Wong LK, Lam W et al. Prognostic use of circulating plasma nucleic acid concentrations in patients with acute stroke. Clin Chem 2003; 49(4): 562– 569.
11. Shapiro B, Chakrabarty M, Cohn EM et al. Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease. Cancer 1983; 51(11): 2116– 2120.
12. Holdenrieder S, Stieber P, Chan LY et al. Cell‑free DNA in serum and plasma:comparison of ELISA and quantitative PCR. Clin Chem 2005; 51(8): 1544– 1546.
13. Diehl F, Li M, Dressman D et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci U S A 2005; 102(45): 16368– 16373.
14. Stroun M, Maurice P, Vasioukhin V et al. The origin and mechanism of circulating DNA. Ann NY Acad Sci 2000; 906: 161– 168.
15. Jung K, Fleischhacker M, Rabien A. Cell‑free DNA in the blood as a solid tumor biomarker – a critical appraisal of the literature. Clin Chim Acta 2010; 411(21– 22): 1611– 1624.
16. Esposito A, Bardelli A, Criscitiello C et al. Monitoring tumor‑ derived cell‑free DNA in patients with solid tumors: clinical perspectives and research opportunities. Cancer Treat Rev 2014; 40(5): 648– 655. doi: 10.1016/ j.ctrv.2013.10.003.
17. Fiegl H, Millinger S, Mueller‑ Holzner E et al. Circulating tumor‑ specific DNA: a marker for monitoring efficacy of adjuvant therapy in cancer patients. Cancer Res 2005; 65(4): 1141– 1145.
18. Gall TM, Frampton AE, Krell J et al. Cell‑free DNA for the detection of pancreatic, liver and upper gastrointestinal cancers: has progress been made? Future Oncol 2013; 9(12): 1861– 1869. doi: 10.2217/ fon.13.152.
19. Diehl F, Schmidt K, Choti MA et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008; 14(9): 985– 990. doi: 10.1038/ nm.1789.
20. Dušek L, Mužík J, Kubásek M et al (eds). Epidemiologie zhoubných nádorů v České republice [monografie na Internetu]. Brno: Masarykova univerzita; 2005 [citováno 1. března 2015]. Dostupný z: http:/ / www.svod.cz.
21. Leung WK, To KF, Man EP et al. Quantitative detection of promoter hypermethylation in multiple genes in the serum of patients with colorectal cancer. Am J Gastroenterol 2005; 100(10): 2274– 2279.
22. Wallner M, Herbst A, Behrens A et al. Methylation of serum DNA is an independent prognostic marker in colorectal cancer. Clin Cancer Res 2006; 12(24): 7347– 7352.
23. Lofton‑ Day C, Model F, Devos T et al. DNA methylation biomarkers for blood‑based colorectal cancer screening. Clin Chem 2008; 54(2): 414– 423.
24. deVos T, Tetzner R, Model F et al. Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem 2009; 55(7): 1337– 1346. doi: 10.1373/ clinchem.2008.115808.
25. Lefebure B, Charbonnier F, Di Fiore F et al. Prognostic value of circulating mutant DNA in unresectable metastatic colorectal cancer. Ann Surg 2010; 251(2): 275– 280. doi: 10.1097/ SLA.0b013e3181c35c87.
26. Kopreski MS, Benko FA, Kwee C et al. Detection of mutant K‑ ras DNA in plasma or serum of patients with colorectal cancer. Br J Cancer 1997; 76(10): 1293– 1299.
27. Bettegowda C, Sausen M, Leary RJ et al. Detection of circulating tumor DNA in early‑ and late‑ stage human malignancies. Sci Transl Med 2014; 6(224): 224ra24. doi: 10.1126/ scitranslmed.3007094.
28. Trevisiol C, Di Fabio F, Nascimbeni R et al. Prognostic value of circulating KRAS2 gene mutations in colorectal cancer with distant metastases. Int J Biol Markers 2006; 21(4): 223– 228.
29. Wong AL, Lim JS, Sinha A et al. Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treatedwith regorafenib. J Transl Med 2015; 13(1): 57. doi: 10.1186/ s12967‑ 015‑ 0405‑ 4.
30. Diehl F, Li M, Dressman D et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci U S A 2005; 102(45): 16368– 16373.
31. Ito T, Kaneko K, Makino R et al. Clinical significance in molecular detection of p53 mutation in serum of patients with colorectal carcinoma. Oncol Rep 2003; 10(6): 1937– 1942.
32. Lindforss U, Zetterquist H, Papadogiannakis N et al. Persistence of K‑ ras mutations in plasma after colorectal tumor resection. Anticancer Res 2005; 25(1B): 657– 661.
33. Kuo YB, Chen JS, Fan CW et al. Comparison of KRAS mutation analysis of primary tumors and matched circulating cell‑free DNA in plasmas of patients with colorectal cancer. Clin Chim Acta 2014; 433: 284– 289.
34. Morgan SR, Whiteley J, Donald E et al. Comparison of KRAS mutation assessment in tumor DNA and circulating free DNA in plasma and serum samples. Clin Med Insights Pathol 2012; 5: 15– 22. doi: 10.4137/ CPath.S8798.
35. Spindler KL, Pallisgaard N, Andersen RF et al. Circulating free DNA as biomarker and source for station detection in metastatic colorectal cancer. PLoS One 2015; 10(4): e0108247. doi: 10.1371/ journal.pone.0108247.
36. Diaz LA Jr, Williams RT, Wu J et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 2012; 486(7404): 537– 540. doi: 10.1038/ nature11219.
37. Spindler KL, Pallisgaard N, Vogelius I et al. Quantitative cell‑free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancerduring treatment with cetuximab and irinotecan. Clin Cancer Res 2012; 18(4): 1177– 1185. doi: 10.1158/ 1078- 0432.CCR‑ 11‑ 0564.
38. Mouliere F, El Messaoudi S, Gongora C et al. Circulating cell‑free DNA from colorectal cancer patients may reveal high KRAS or BRAF mutation load. Transl Oncol 2013; 6(3): 319– 328.
39. Frattini M, Gallino G, Signoroni S. Quantitative analysis of plasma DNA in colorectal cancer patients: a novel prognostic tool. Ann NY Acad Sci 2006; 1075: 185– 190.
40. Schwarzenbach H, Stoehlmacher J, Pantel K et al. Detection and monitoring of cell‑free DNA in blood of patients with colorectal cancer. Ann N Y Acad Sci 2008; 1137: 190– 196. doi: 10.1196/ annals.1448.025.
41. De Roock W, Biesmans B, De Schutter J et al. Clinical biomarkers in oncology: focus on colorectal cancer. Mol Diagn Ther 2009; 13(2): 103– 114. doi: 10.2165/ 01250444‑ 200913020‑ 00004.
42. Sozzi G, Conte D, Mariani L et al. Analysis of circulating tumor DNA in plasma at diagnosis and during follow‑up of lung cancer patients. Cancer Res 2001; 61(12): 4675– 4678.
43. Gautschi O, Huegli B, Ziegler A et al. Origin and prognostic value of circulating KRAS mutations in lung cancer patients. Cancer Lett 2007; 254(2): 265– 273.
44. Govindan R, Page N, Morgensztern D et al. Changing epidemiology of small‑cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006; 24(28): 4539– 4544.
45. Gazdar AF. Activating and resistance mutations of EGFR in non‑small‑cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene 2009; 28 (Suppl 1): S24– S31. doi: 10.1038/ onc.2009.198.
46. Bai H, Mao L, Wang HS et al. Epidermal growth factor receptor mutations in plasma DNA samples predict tumor response in Chinese patients with stages IIIB to IV non‑small‑cell lung cancer. J Clin Oncol 2009; 27(16): 2653– 2659. doi: 10.1200/ JCO.2008.17.3930.
47. Kuang Y, Rogers A, Yeap BY et al. Noninvasive detection of EGFR T790M in gefitinib or erlotinib resistant non‑small cell lung cancer. Clin Cancer Res 2009; 15(8): 2630– 2636. doi: 10.1158/ 1078‑ 0432.CCR‑ 08‑ 2592.
48. Mack PC, Holland WS, Burich RA et al. EGFR mutations detected in plasma are associated with patient outcomes in erlotinib plus docetaxel‑treated non‑small cell lung cancer. J Thorac Oncol 2009; 4(12): 1466– 1472. doi: 10.1097/ JTO.0b013e3181bbf239.
49. Young TK, Chan KC, Mok TS et al. Single‑molecule detection of epidermalgrowth factor receptor mutations in plasma by microfluidics digital PCR in non‑small cell lung cancer patients. Clin Cancer Res 2009; 15(6): 2076– 2084. doi: 10.1158/ 1078‑ 0432.CCR‑ 08‑ 2622.
50. Camps C, Jantus‑ Lewintre E, Cabrera A et al. The identification of KRAS mutations at codon 12 in plasma DNA is not a prognostic factor in advanced non‑small cell lung cancer patients. Lung Cancer 2011; 72(3): 365– 369. doi: 10.1016/ j.lungcan.2010.09.005.
51. Nygaard AD, Garm Spindler KL, Pallisgaard N et al. The prognostic value of KRAS mutated plasma DNA in advanced non‑small cell lung cancer. Lung Cancer 2013; 79(3): 312– 317. doi: 10.1016/ j.lungcan.2012.11.016.
52. Gonzalez R, Silva JM, Sanchez A et al. Microsatellite alterations and TP53 mutations in plasma DNA of small‑cell lung cancer patients: follow‑up study and prognostic significance. Ann Oncol 2000; 11(9): 1097– 1104.
53. Brevet M, Johnson ML, Azzoli CG et al. Detection of EGFR mutations in plasma DNA from lung cancer patients by mass spectrometry genotyping is predictive of tumor EGFR status and response to EGFR inhibitors. Lung Cancer 2011; 73(1): 96– 102. doi: 10.1016/ j.lungcan.2010.10.014.
54. Pan SY, Xie EF, Shu YQ et al. Methylation quantification of adenomatous polyposis coli (APC) gene promoter in plasma of lung cancerpatients. Ai Zheng 2009; 28(4): 384– 389.
55. Powrózek T, Krawczyk P, Kucharczyk T et al. Septin 9 promoter region methylation in free circulating DNA‑ potential role in noninvasive diagnosis of lung cancer: preliminary report. Med Oncol 2014; 31(4): 917. doi: 10.1007/ s12032‑ 014‑ 0917‑ 4.
56. Ponomaryova AA, Rykova EY, Cherdyntseva NV et al. Potentialities of aberrantly methylated circulating DNA for diagnostics and post‑treatment follow‑up of lung cancer patients. Lung Cancer 2013; 81(3): 397– 403. doi: 10.1016/ j.lungcan.2013.05.016.
57. Hoffmann AC, Kaifi JT, Vallböhmer D et al. Lack of prognostic signifikance of serum DNA methylation of DAPK, MGMT, and GSTPI in patients with non‑small cell lung cancer. J Surg Oncol 2009; 100(5): 414– 417. doi: 10.1002/ jso.21348.
58. Esteller M, Sanchez‑ Cespedes M, Rosell R et al. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non‑small cell lung cancer patients. Cancer Res 1999; 59(1): 67– 70.
59. Sozzi G, Conte D, Leon M et al. Quantification of free circulating DNA as a diagnostic marker in lung cancer. J Clin Oncol 2003; 21(21): 3902– 3908.
60. Paci M, Maramotti S, Bellesia E et al. Circulating plasma DNA as diagnostic biomarker in non‑small cell lung cancer. Lung Cancer 2009; 64(1): 92– 97. doi: 10.1016/ j.lungcan.2008.07.012.
61. Szpechcinski A, Dancewicz M, Kopinski P et al. Real‑ time PCR quantification of plasma DNA in non‑small cell lung cancer patients and healthy controls. Eur J Med Res 2009; 14 (Suppl 4): 237– 240.
62. Herrera LJ, Raja S, Gooding WE et al. Quantitative analysis of circulating plasma DNA as a tumor marker in thoracic malignancies. Clin Chem 2005; 51(1): 113– 118.
63. Fackler MJ, Lopez Bujanda Z, Umbricht C et al. Novel methylated biomarkers and a robust assay to detect circulating tumor DNA in metastatic breast. Cancer Res 2014; 74(8): 2160– 2170.
64. Fiegl H, Millinger S, Mueller‑ Holzner E et al. Circulating tumor‑ specific DNA: a marker for monitoring efficacy of adjuvant therapy in cancer patients. Cancer Res 2005; 65(4): 1141– 1145.
65. Muller HM, Widschwendter A, Fiegl H et al. DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res 2003; 63(22): 7641– 7645.
66. Agostini M, Enzo MV, Bedin C et al. Circulating cell‑free DNA: a promising marker of regional lymphonode metastasis in breast cancer patients. Cancer Biomark 2012; 11(2– 3): 89– 98.
67. Yazici H, Terry MB, Cho YH et al. Aberrant methylation of RASSF1A in plasma DNA before breast cancer diagnosis in the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev 2009; 18(10): 2723– 2725. doi: 10.1158/ 1055‑ 9965.EPI‑ 08‑ 1237.
68. Liggett TE, Melnikov AA, Marks JR et al. Methylation patterns in cell‑free plasma DNA reflect removal of the primary tumor and drug treatment of breast cancer patients. Int J Cancer 2011; 128(2): 492– 499. doi: 10.1002/ ijc.25363.
69. Mirza S, Sharma G, Prasad CP et al. Promoter hypermethylation of TMS1, BRCA1, ERalpha and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients. Life Sci 2007; 81(4): 280– 287.
70. Mirza S, Sharma G, Parshad R et al. Clinical significance of promoter hypermethylation of ERβ and RARβ2 in tumor and serum DNA in Indian breast cancer patients. Ann Surg Oncol 2012; 19(9): 3107– 3115. doi: 10.1245/ s10434‑ 012‑ 2323‑ 5.
71. Sharma G, Mirza S, Parshad R et al. DNA methylation of circulating DNA: a marker for monitoring efficacy of neoadjuvant chemotherapy in breast cancer patients. Tumour Biol 2012; 33(6): 1837– 1843. doi: 10.1007/ s13277‑ 012‑ 0443‑ y.
72. Hoque MO, Feng Q, Toure P et al. Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer. J Clin Oncol 2006; 24(26): 4262– 4269.
73. Board RE, Wardley AM, Dixon JM et al. Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer. Breast Cancer Res Treat 2010; 120(2): 461– 467. doi: 10.1007/ s10549‑ 010‑ 0747‑ 9.
74. Higgins MJ, Jelovac D, Barnathan E et al. Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood. Clin Cancer Res 2012; 18(12): 3462– 3469.
75. Shao ZM, Wu J, Shen ZZ et al. p53 mutation in plasma DNA and its prognostic value in breast cancer patients. Clin Cancer Res 2001; 7(8): 2222– 2227.
76. Page K, Hava N, Ward B et al. Detection of HER2 amplification in circulating free DNA in patients with breast cancer. Br J Cancer 2011; 104(8): 1342– 1348. doi: 10.1038/ bjc.2011.89.
77. Bechmann T, Andersen RF, Pallisgaard N et al. Plasma HER2 amplification in cell‑free DNA during neoadjuvant chemotherapy in breast cancer. J Cancer Res Clin Oncol 2013; 139(6): 995– 1003. doi: 10.1007/ s00432‑ 013‑ 1413‑ 5.
78. Shaw JA, Smith BM, Walsh T et al. Microsatellite alterations plasma DNA of primary breast cancer patients. Clin Cancer Res 2000; 6(3): 1119– 1124.
79. Schwarzenbach H, Eichelser C, Kropidlowski J et al. Loss of heterozygosity at tumor suppressor genes detectable on fractionated circulating cell‑free tumor DNA as indicator of breast cancer progression. Clin Cancer Res 2012; 18(20): 5719– 5730. doi: 10.1158/ 1078‑ 0432.CCR‑ 12‑ 0142.
80. Huang ZH, Li LH, Hua D. Quantitative analysis of plasma circulating DNA at diagnosis and during follow‑up of breast cancer patients. Cancer Lett 2006; 243(1): 64– 70.
81. Catarino R, Ferreira MM, Rodrigues H et al. Quantification of free circulating tumor DNA as a diagnostic marker for breast cancer. DNA Cell Biol 2008; 27(8): 415– 421. doi: 10.1089/ dna.2008.0744.
82. Kohler C, Radpour R, Barekati Z et al. Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors. Mol Cancer 2009; 8: 105. doi: 10.1186/ 1476‑ 4598‑ 8‑ 105.
83. Nicolini C, Ens C, Cerutti T et al. Elevated level of cell free plasma DNA is associated with advanced stage breast cancer and metastasi. Clin Chem Lab Med 2013; 51(11): 277– 278. doi: 10.1515/ cclm‑ 2013‑ 0120.
84. Campbell IG, Russell SE, Choong DY et al. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 2004; 64(21): 7678– 7681.
85. Dehan P, Kustermans G, Guenin S et al. DNA methylation and cancer diagnosis: new methods and applications. Expert Rev Mol Diagn 2009; 9(7): 651– 657. doi: 10.1586/ erm.09.53.
86. Hohaus S, Giachelia M, Massini G et al. Cell‑free circulating DNA in Hodgkin‘s and non‑Hodgkin‘s lymphomas. Ann Oncol 2009; 20(8): 1408– 1413. doi: 10.1093/ annonc/ mdp006.
87. Mussolin L, Burnelli R, Pillon M et al. Plasma cell‑free DNA in paediatric lymphomas. J Cancer 2013; 4(4): 323– 329. doi: 10.7150/ jca.6226.
88. Frickhofen N, Müller E, Sandherr M et al. Rearranged Ig heavy chain DNA is detectable in cell‑free blood samples of patients with B‑ cell neoplasia. Blood 1997; 90(12): 4953– 4960.
89. Hosny G, Farahat N, Hainaut P. TP53 mutations in circulating free DNA from Egyptian patients with non‑Hodgkin‘s lymphoma. Cancer Lett 2009; 275(2): 234– 239. doi: 10.1016/ j.canlet.2008.10.029.
90. Zhong L, Huang WF. Better detection of Ig heavy chain and TCRγ gene rearrangement in plasma cell‑free DNA from patients with non‑Hodgkin lymphoma. Neoplasma 2010; 57(6): 507– 511.
91. Armand P, Oki Y, Neuberg DS et al. Detection of circulating tumour DNA in patients with aggressive B‑ cell non‑Hodgkin lymphoma. Br J Haematol 2013; 163(1): 123– 126. doi: 10.1111/ bjh.12439.
92. He J, Wu J, Jiao Y et al. IgH gene rearrangements as plasma biomarkers in non‑ Hodgkin‘s lymphoma patients. Oncotarget 2011; 2(3): 178– 185.
93. Kurlander R, LI Y, Stetler‑ Stevenson M et al. Evaluation of circulating cell‑ free VDJ DNA as a marker for monitoring patients with multiple myeloma (MM) during treatment with carfilzomib, lenalidomide and dexamethasone. In: American Society of Hematology 2013 Annual Meeting. Abstr. 1868 (Poster Presentation).
94. Kubiczkova‑ Besse L, Drandi D, Sedlarikova L et al. Cell‑free DNA for minimal residual disease monitoring in multiple myeloma. In: American Society of Hematology 2014 Annual Meeting. Abstract 3423 (Poster Presentation).
95. Schwarz AK, Stanulla M, Cario G et al. Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia. Ann Hematol 2009; 88(9): 897– 905. doi: 10.1007/ s00277‑ 009‑ 0698‑ 6.
96. Gao YJ, He YJ, Yang ZL et al. Increased integrity of circulating cell‑free DNA in plasma of patients with acute leukemia. Clin Chem Lab Med 2010; 48(11): 1651– 1656. doi: 10.1515/ CCLM.2010.311.
97. Jiang Y, Pan SY, Xia WY et al. Dynamic monitoring of plasma circulating DNA in patients with acute myeloid leukemia and its clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2012; 20(1): 53– 56.
98. Quan J, Gao YJ, Yang ZL et al. Quantitative detection of circulating nucleophosmin mutations DNA in the plasma of patients with acute myeloidleukemia. Int J Med Sci 2015; 12(1): 17– 22. doi: 10.7150/ ijms.10144.
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