Detection of a Hodgkin/Reed‐Sternberg cell specific immunoglobulin gene rearrangement in the serum DNA of a patient with Hodgkin's disease

Kornacker, Martin; Jox, Andrea; Vockerodt, Martina; Tesch, Hans; Bohlen, Heribert; Diehl, Volker; Wolf, Juergen

doi:10.1046/j.1365-2141.1999.01564.x

Cited by 16 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The identification of identical Hodgkin Reed-Sternberg immunoglobulin gene rearrangements in biopsy and serum samples shows that circulating Hodgkin Reed-Sternberg cells are present in the peripheral blood (8). Consistent with the notion that cell-free viral DNA may be shed from circulating apoptotic malignant cells, it has been shown that cell-free DNA is present as ''naked'' DNA rather than as virions (9).…”

Section: Latent Ebv Genomes Are Found In the Malignant Hodgkinmentioning

confidence: 48%

Plasma Epstein-Barr Virus (EBV) DNA Is a Biomarker for EBV-Positive Hodgkin's Lymphoma

Gandhi

Lambley

Burrows

et al. 2006

Clinical Cancer Research

117

View full text Add to dashboard Cite

Purpose: Latent Epstein-Barr virus (EBV) genomes are found in the malignant cells of approximately one-third of Hodgkin's lymphoma (HL) cases. Detection and quantitation of EBV viral DNA could potentially be used as a biomarker of disease activity. Experimental Design: Initially, EBV-DNA viral load was prospectively monitored from peripheral blood mononuclear cells (PBMC) in patients with HL. Subsequently, we analyzed viral load in plasma from a second cohort of patients. A total of 58 patients with HL (31 newly diagnosed, 6 relapsed, and 21 in long-term remission) were tested. Using real-time PCR, 43 PBMC and 52 plasma samples were analyzed. Results: EBV-DNA was detectable in the plasma of all EBV-positive patients with HL prior to therapy. However, viral DNA was undetectable following therapy in responding patients (P = 0.0156), EBV-positive HL patients in long-term remission (P = 0.0011), and in all patients with EBV-negative HL (P = 0.0238). Conversely, there was no association seen for the EBV-DNA load measured from PBMC in patients with active EBV-positive HL patients as compared with EBV-negative HL, or patients in long-term remission. EBV-DNA load in matched plasma/PBMC samples were not correlated. Conclusions: We show that free plasma EBV-DNA has excellent sensitivity and specificity, and can be used as a noninvasive biomarker for EBV-positive HL and that serial monitoring could predict response to therapy. Additional prospective studies are required to further evaluate the use of free plasma EBV-DNA as a biomarker for monitoring response to treatment in patients with EBV-positive HL.

show abstract

Section: Latent Ebv Genomes Are Found In the Malignant Hodgkinmentioning

confidence: 48%

Plasma Epstein-Barr Virus (EBV) DNA Is a Biomarker for EBV-Positive Hodgkin's Lymphoma

Gandhi

Lambley

Burrows

et al. 2006

Clinical Cancer Research

117

View full text Add to dashboard Cite

show abstract

“…Unlike PTLD, the significant correlation of plasma/serum viral load with therapeutic response does not appear to hold if PBMC are used as the source to measure EBV DNA [117] (GANDHI & KHANNA, UNPUBLISHED OBSERVATIONS), which is consistent with the source of viral DNA from HRS cells that have been shed into the periphery, rather than viral replication at other sites. The identification of identical HRS Ig gene rearrangements in biopsy and serum samples demonstrates that HRS cells do shed DNA into peripheral blood [118]. This notion is further supported by the use of DNase digestion to plasma/serum samples, which demonstrate that the detected viral DNA in HL patients is 'naked' rather than from packaged viral particles; the latter would be expected if active viral replication were taking place [117].…”

Section: Hodgkin's Lymphomamentioning

confidence: 70%

Epstein–Barr virus-associated lymphomas

Gandhi

2006

Expert Review of Anti-infective Therapy

View full text Add to dashboard Cite

Following Epstein and colleagues' ground-breaking discovery of Epstein-Barr virus by electron microscopy of Burkitt's lymphoma cell lines, there came the observation that Epstein-Barr virus induces immortalization of B cells in vitro. Thus, initial hopes were of a virus confined to equatorial Africa with a causal link to a particular subtype of childhood lymphoma. Over the past 40 years there has been great progress towards understanding the biology and epidemiology of Epstein-Barr virus, which conclusively show that these early ideas were overly simplistic. It is now known that Epstein-Barr virus has a seroprevalence of approximately 95% worldwide, and persists for life within host B lymphocytes. Infection in New World primates leads to lymphoma and inoculation of peripheral blood mononuclear cells from Epstein-Barr virus-seropositive subjects into severe combined immunodeficiency mice results in B-cell lymphoproliferative disorders. Epstein-Barr virus is now known to be implicated in a range of lymphoid and other malignancies, and this association will be the subject of this review.

show abstract

“…In addition, EBV DNA in serum of Hodgkin's disease patients has been shown to bè naked DNA' rather than viral particles, suggesting that tumour cells are the main source of the circulating EBV DNA (Gallagher et al, 1999). Indeed, identical Hodgkin/Reed±Sternberg cell-specific immunoglobulin gene rearrangements in serum and biopsy samples have been demonstrated in a patient with Hodgkin's disease (Kornacker et al, 1999). This further supports the contention that tumour-derived DNA sequences are released from tumour cells into the circulation.…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of circulating cell-free Epstein-Barr virus (EBV) DNA levels in patients with EBV-associated lymphoid malignancies

Lei¹,

Chan²,

Chan³

et al. 2000

Br J Haematol

103

View full text Add to dashboard Cite

Cell-free Epstein-Barr virus (EBV) DNA has recently been detected in the plasma and serum of patients with Hodgkin's disease, post-transplant lymphoproliferative disease (PTLD) and acquired immunodeficiency syndrome-related lymphoma. However, no data are available on the temporal variation of plasma/serum EBV DNA levels in patients with EBV-associated lymphoid malignancies during the course of therapy. Using a real-time quantitative polymerase chain reaction assay, we studied the plasma EBV DNA levels in 13 patients with EBV-associated lymphoid malignancies (six patients with Hodgkin's disease, four with nasal natural killer/T-cell lymphoma, two cases of PTLD and one patient with Burkitt's lymphoma) at presentation and during therapy. Plasma EBV DNA was detected in 12 of the 13 patients (median 2,266 copies/ml; interquartile range 181-8,379 copies/ml), but not in any of 35 healthy control subjects (P < 0.0001). The EBV status in tumour cells was also examined in 12 of these patients using in situ hybridization for EBV-encoded small RNAs (EBERs). EBER positivity was observed in 11 patients, all of whom had EBV DNA detectable in plasma. The one patient who had no detectable plasma EBV DNA was also negative for EBERs in tumour tissue. Serial measurements of plasma EBV DNA levels were performed in nine of the patients during the course of therapy. All patients who responded to therapy demonstrated a significant reduction of plasma EBV DNA to low or undetectable levels, whereas in two patients with ineffective therapy, disease progression was associated with a rapid increase in plasma EBV DNA levels. We concluded that plasma EBV DNA is detectable in a wide range of EBV-associated lymphoid malignancies. As plasma EBV DNA levels correlate well with the therapeutic response, such analysis may be a valuable tool for monitoring clinical progress.

show abstract

Detection of a Hodgkin/Reed‐Sternberg cell specific immunoglobulin gene rearrangement in the serum DNA of a patient with Hodgkin's disease

Cited by 16 publications

References 10 publications

Plasma Epstein-Barr Virus (EBV) DNA Is a Biomarker for EBV-Positive Hodgkin's Lymphoma

Plasma Epstein-Barr Virus (EBV) DNA Is a Biomarker for EBV-Positive Hodgkin's Lymphoma

Epstein–Barr virus-associated lymphomas

Quantitative analysis of circulating cell-free Epstein-Barr virus (EBV) DNA levels in patients with EBV-associated lymphoid malignancies

Contact Info

Product

Resources

About