Circulating Epstein-Barr virus DNA and cell-free DNA in pediatric lymphomas

Background and objectives. Quantification of serum Epstein–Barr virus (EBV) DNA and/or cell-free total DNA (cf-DNA) may become valuable sources for prognosis evaluation and monitoring treatment response in lymphomas. We aimed to investigate their roles as potential markers in pediatric Hodgkin (HL) and nonHodgkin lymphomas (NHL). Method. Between the years 2005–2008, 34 patients with HL and 45 with NHL were prospectively included. Serum samples were collected upon diagnosis, after 1-3 and 4-6 months and at the end of treatment, or at disease recurrence. RT-PCR determination of cf-DNA and EBV DNA were performed using amplification of BAMH1W region of EBV genome and of human β-globin gene. Results were analyzed for correlation with clinical and pathological characteristics. Results. Median ages were 8.9 years for HL and 8.8 years for NHL cases. Twenty-three healthy children cured from various childhood cancers served as the control group. In the controls, median serum EBV DNA copy number was ‘0’ and median serum cf-DNA level was 50 ng/ml. At initial diagnosis, serum EBV DNA copy numbers were elevated in 20/34 HL and 8/45 NHL cases (p

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1. Gandhi MK, Lambley E, Burrows J, et al. Plasma Epstein-Barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin's lymphoma. Clin Cancer Res 2006; 12: 460-464.

2. Spacek M, Hubacek P, Markova J, et al. Plasma EBVDNA monitoring in Epstein-Barr virus-positive Hodgkin lymphoma patients. APMIS 2011; 119: 10- 16.

3. Dinand V, Sachdeva A, Datta S, et al. Plasma Epstein Barr virus (EBV) DNA as a biomarker for EBV associated Hodgkin lymphoma. Indian Pediatr 2015; 52: 681-665.

4. Lei KI, Chan LY, Chan WY, Johnson PJ, Lo YM. Quantitative analysis of circulating cell-free EpsteinBarr virus (EBV) DNA levels in patients with EBVassociated lymphoid malignancies. Br J Haematol 2000; 171: 239-246.

5. Au WY, Pang A, Choy C, Chim CS, Kwong YL. Quantification of circulating Epstein-Barr virus (EBV) DNA in the diagnosis and monitoring of natural killer cell and EBV-positive lymphomas in immunocompetent patients. Blood 2004; 104: 243- 249.

6. Kabyemera R, Masalu N, Rambau P, et al. Relationship between non-Hodgkin's lymphoma and blood levels of Epstein-Barr virus in children in North-Western Tanzania: a case control study. BMC Pediatr 2013; 13: 4.

7. Anker P, Stroun M. Circulating DNA in plasma or serum. Medicina (B Aires) 2000; 60(5 Pt 2): 699-702.

8. Schwarzenbach H, Hoon DSB, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011; 11: 426-437.

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

10. Vendrell JA, Mau-Them FT, Béganton B, Godreuil S, Coopman P, Solassol J. Circulating cell free tumor DNA detection as a routine tool for lung cancer patient management. Int J Mol Sci 2017; 18: 264.

11. Kurihara S, Ueda Y, Onitake Y, et al. Circulating free DNA as non-invasive diagnostic biomarker for childhood solid tumors. J Pediatr Surg 2015; 50: 2094-2097.

12. Machado ASC, Da Silva Robaina MC, Magalhães De Rezende LM, et al. Circulating cell free and Epstein-Barr virus DNA in pediatric B-non-Hodgkin lymphomas. Leuk Lymphoma 2010; 51: 1020-1027.

13. Hohaus S, Giachelia M, Massini G, et al. Cell-free circulating DNA in Hodgkin's and non-Hodgkin's lymphomas. Ann Oncol 2009; 20: 1408-1413.

14. Mussolin L, Burnelli R, Pillon M, et al. Plasma cellfree DNA in paediatric lymphomas. J Cancer 2013; 4: 323-329.

15. Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-481.

16. Zhang W, Chen Y, Chen L, et al. The clinical utility of plasma Epstein-Barr virus DNA assays in nasopharyngeal carcinoma: the dawn of a new era?: a systematic review and meta-analysis of 7836 cases. Medicine (Baltimore) 2015; 94: e845.

17. Glaser SL, Lin RJ, Stewart SL, et al. Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data. Int J Cancer 1997; 70: 375-382.

18. Cavdar AO, Pamir A, Gözdaşoglu S, et al. Hodgkin disease in children: clinicoepidemiologic and viral (Epstein-Barr virus) analyses. Med Pediatr Oncol 1999; 32: 18-24.

19. Zhou XG, Sandvej K, Li PJ, et al. Epstein-Barr virus (EBV) in Chinese pediatric Hodgkin disease: Hodgkin disease in young children is an EBVrelated lymphoma. Cancer 2001; 92: 1621-1631.

20. Dinand V, Dawar R, Arya LS, Unni R, Mohanty B, Singh R. Hodgkin's lymphoma in Indian children: prevalence and significance of Epstein-Barr virus detection in Hodgkin's and Reed-Sternberg cells. Eur J Cancer 2007; 43: 161-168.

21. Gallagher A, Armstrong AA, MacKenzie J, et al. Detection of Epstein-Barr virus (EBV) genomes in the serum of patients with EBV-associated Hodgkin's disease. Int J Cancer 1999; 84: 442-448.

22. Pajand O, Pourakbari B, Mahjob F, Aghamohammadi A, Mamishi N, Mamishi S. Detection of EpsteinBarr virus DNA in plasma and lymph node biopsy samples of pediatric and adult patients with Hodgkin lymphoma. Pediatr Hematol Oncol 2011; 28: 10-15.

23. Musacchio JG, Carvalho Mda G, Morais JC, et al. Detection of free circulating Epstein-Barr virus DNA in plasma of patients with Hodgkin's disease. Sao Paulo Med J 2006; 124: 154-157.

24. Park JH, Yoon DH, Kim S, et al. Pretreatment whole blood Epstein-Barr virus-DNA is a significant prognostic marker in patients with Hodgkin lymphoma. Ann Hematol 2016; 95: 801-808.

25. Kanakry J, Ambinder R. The biology and clinical utility of EBV monitoring in blood. Curr Top Microbiol Immunol 2015; 391: 475-499.

26. Jones K, Nourse JP, Keane C, et al. Tumor-specific but not nonspecific cell-free circulating DNA can be used to monitor disease response in lymphoma. Am J Hematol 2012; 87: 258-265.

27. Reiter A, Schrappe M, Tiemann M, et al. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: a report of the Berlin-Frankfurt-Münster Group Trial NHLBFM 90. Blood 1999; 94: 3294-3306.

28. 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: 897-905.

29. Primerano S, Burnelli R, Carraro E, et al. Kinetics of circulating plasma cell-free DNA in paediatric classical Hodgkin lymphoma. J Cancer 2016; 7: 364- 366.
Turkish Journal of Pediatrics-Cover
  • ISSN: 0041-4301
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 1958
  • Yayıncı: Hacettepe Üniversitesi Çocuk Sağlığı Enstitüsü Müdürlüğü
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