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. 2013 Apr 16;4(4):323-9.
doi: 10.7150/jca.6226. Print 2013.

Plasma cell-free DNA in paediatric lymphomas

Lara Mussolin  1 , Roberta Burnelli, Marta Pillon, Elisa Carraro, Piero Farruggia, Alessandra Todesco, Maurizio Mascarin, Angelo Rosolen
Affiliations

Plasma cell-free DNA in paediatric lymphomas

Lara Mussolin et al. J Cancer. .

Abstract

Background: Extracellular circulating DNA (cfDNA) can be found in small amounts in plasma of healthy individuals. Increased levels of cfDNA have been reported in patients with cancer of breast, cervix, colon, liver and it was shown that cfDNA can originate from both tumour and non-tumour cells.

Objectives: Levels of cfDNA of a large series of children with lymphoma were evaluated and analyzed in relation with clinical characteristics.

Methods: plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients. Wilcoxon rank sum test was used to compare plasma levels among different patient subgroups and controls and to analyze relationship between levels of cfDNA and clinical characteristics.

Results: Levels of cfDNA in lymphoma patients were significantly higher compared with controls (p<0.0001). CfDNA was associated with median age (p=0.01) in HL, and with stage in ALCL (p=0.01). In HL patients high cfDNA levels were correlated with poor prognosis (p=0.03). In ALCL we found that most of the cfDNA (77%) was non-tumor DNA.

Conclusion: level of plasma cfDNA might constitute an important non-invasive tool at diagnosis in lymphoma patients' management; in particular in patients with HL, cfDNA seems to be a promising prognostic biomarker.

Keywords: Hodgkin.; cfDNA; childhood; lymphoma; prognosis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Box-plots of cell-free DNA plasma concentrations in healthy controls and patients with lymphoma at diagnosis. The upper border of the box indicates the upper quartile (75th percentile) while the lower border indicates the lower quartile (25th percentile), and the horizontal line in the box the median. ALCL, Anaplastic Large Cell Lymphoma; HL, Hodgkin Lymphoma; BL, Burkitt Lymphoma; DLBCL, Diffuse Large B Cell Lymphoma; LBL, Lymphoblastic Lymphoma. Maximun values: ALCL, 2034 ng/mL; HL, 1650 ng/mL: DLBCL, 700ng/mL; LBL, 360ng/mL;BL, 3660 ng/mL.
Figure 2
Figure 2
Distribution of cfDNA in 43 ALCL plasma patients using 2 probes:POLR2 probe for tumor-derived and non-tumor derived cfDNA (white color); NPM-ALK probe specific only for tumor-derived cfDNA (black color). cfDNA=cell free DNA.
Figure 3
Figure 3
Event Free Survival (EFS) in 43 HL patients according to the DNA plasma concentration (median value cfDNA= 46ng/mL) at diagnosis. EFS was 92% (±6) for patients with cfDNA≤ 46ng/mL and 60% (±18%) for patients with cfDNA> 46ng/mL (p=0.03).
See this image and copyright information in PMC

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