Circulating cell-free and Epstein–Barr virus DNA in pediatric B-non-Hodgkin lymphomas

Abstract

Tumor-derived DNA is elevated in the plasma of patients with cancer. The analysis of circulating DNA may be useful for diagnosis, prognosis evaluation, and early detection of disease recurrence. In order to investigate cf-DNA as a marker during treatment, we serially quantified total cell-free (cf) and EBV plasma DNA in 30 cases of pediatric B-non-Hodgkin lymphoma by real-time PCR. The cf-DNA levels were significantly increased in patient samples at diagnosis as compared with the healthy controls (p < 0.001). At the end of treatment, a significant decrease in plasma DNA concentration was observed as compared with values observed at diagnosis (median: 94.0 copies/mL, p = 0.001). EBV was detected by ISH in 7/30 patients. Plasma EBV DNA levels were obtained from seven EBV-positive patients (median: 1278 copies/mL), while EBV DNA was not detected in 23 EBV-negative patients and 10 healthy controls. The association between the two methods of detection was statistically significant, with 100% correlation (Kappa coefficient, p = 1). In addition, the decrease of EBV viral load was associated with therapy response. Quantification of plasma EBV DNA may become a valuable source for disease detection of pediatric EBV-associated lymphomas and for monitoring treatment response.

Keywords:

• Cell-free DNA
• circulating DNA
• Epstein–Barr virus
• quantitative PCR
• viral load
• B-non-Hodgkin lymphoma

Acknowledgements

We acknowledge the cooperation of all patients, their parents, and physicians who contributed to the collection of samples for this study.

Declaration of interest: This work was supported by grants from Swiss Bridge Foundation, Switzerland, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) – Processo No. 400801/2005-1, and FAPERJ-APQ1-Processo E-26/171.479/2006.