Cell-free circulating DNA in Hodgkin's and non-Hodgkin's lymphomas

Istituto di Ematologia e di Anatomia Patologica, Università Cattolica S. Cuore, Rome, Italy.
Annals of Oncology (Impact Factor: 7.04). 05/2009; 20(8):1408-13. DOI: 10.1093/annonc/mdp006
Source: PubMed


Levels of cell-free circulating DNA have been correlated to clinical characteristics and prognosis in patients with cancers of epithelial origin, while there are no data on patients with B-lymphoproliferative diseases.
Cell-free DNA levels in the plasma samples of 142 patients with lymphomas [45 with Hodgkin's lymphoma (HL), 63 with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL), 24 with follicular, and 10 with mantle cell non-Hodgkin's lymphoma (NHL)] at diagnosis and of 41 healthy individuals were determined using a quantitative PCR for the beta-globin gene.
Levels of circulating DNA in patients with HL, DLBCL, and mantle cell NHL were significantly higher than in controls (P < 0.01 for all). Increased levels of plasma DNA were associated with advanced stage disease, presence of B-symptoms, elevated lactate dehydrogenase levels, and age >60 years (P = 0.009; <0.0001; <0.0001; 0.04, respectively). In HL, histological signs of necrosis and grade 2 type of nodular sclerosis were associated with increased plasma DNA. Elevated plasma DNA levels were associated with an inferior failure-free survival in patients with HL (P = 0.01) and DLBCL (P = 0.03).
Quantification of circulating DNA by real-time PCR at diagnosis can identify patients with elevated levels that are associated with disease characteristics indicating aggressive disease and poor prognosis.

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    • "Cell-free DNA of cellular and viral origin can be detected in the plasma of patients with HL at diagnosis.50–51 Cell-free DNA is released from the tumor tissue, and levels correlate to disease activity.52 "
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    ABSTRACT: Hodgkin lymphoma (HL) is among the neoplastic diseases that has the best long-term outcome after cytotoxic treatment. Cure rates approach 80-90%; however, 15-20% of patients will be resistant to therapy (primary refractory) or relapse after treatment. Prognostic factors should help to stratify treatment according to the risk profile and identify patients at risk for failure. Significance of prognostic factors partly depends on the efficacy of the treatments administered, since new effective therapies can variably counterbalance the adverse effects of some unfavorable clinical determinants. As a consequence, some prognostic factors thought to be important in the past may become meaningless when modern successful therapies are used. Therefore, the value of prognostic factors has to be updated periodically, and then adapted to new emerging biomarkers. Besides the prognostic role of PET imaging, tissue and circulating biomarkers, as the number of tumor-infiltrating macrophages, cytokine and chemokine levels and profiling of circulating nucleic acids (DNA and microRNAs) have shown promise.
    Mediterranean Journal of Hematology and Infectious Diseases 01/2014; 6(1):e2014053. DOI:10.4084/MJHID.2014.053
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    • "Thus, we hypothesize that the fraction of cfDNA and tumor extension are correlated with small tumors shedding small amount of DNA and larger tumors -that infiltrate the surrounding normal tissues- shedding more DNA, including DNA from adjacent non tumor cells. These data are in agreement with results obtained in adult lymphoma patients.13 "
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    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.
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    ABSTRACT: Plasma cell-free DNA is the soluble DNA and tumor-derived DNA in plasma which has the same mutation as the tumor cellular DNA. This study aimed at comparing the properties of plasma cell-free DNA with the biopsy's DNA in order to evaluate the clinical significance of IgH and TCRγ gene rearrangement in plasma cell-free DNA from patients with non-Hodgkin's Lymphoma. A total of 360 samples were studied. IgH (FR3A/VLJH) and TCRγ (TVG/TJX) were amplified by PCR. Results of plasma cell-free DNA were compared with biopsy's DNA and mononuclear cellular DNA respectively. Plasma cell-free DNA were successfully extracted from 288 cases of newly diagnosed, refractory and relapsed NHL in total 360 patients (80%).But nothing was found in the other 72 remittent patients. The positive percentage of IgH rearrangement in patients with B-NHL was 81% in plasma cell-free DNA and 77% in biopsy's DNA (P>0.05). As to the ratio of TCRγ rearrangement in patients with T-NHL, the former was 44%, and the latter was 39% (P>0.05). These results show tumor-derived DNA could be detected in tumor loaded plasma, even of underlying cancer patients. For NHL patients, detecting IgH and TCRγ gene rearrangement of plasma cell-free DNA has the same clinical significance as biopsy's DNA. Moreover, it's more simple, convenient and non-invasive. Keywords: Lymphoma non-Hodgkin, plasma, cell-free DNA, gene rearrangement, immunoglobulin, heavy-chain gene, T-cell receptor.γ
    Neoplasma 01/2010; 57(6):507-11. DOI:10.4149/neo_2010_06_507 · 1.87 Impact Factor
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