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Updated: Jul 26, 2025
VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
Cell-free DNA for detection of clonal B cells in diffuse large B cell lymphoma by sequencing
Elisabeth Luna Højlund1, Oriane Cédile1,2, Thomas Stauffer Larsen1,3
1Haematology-Pathology Research Laboratory, Research Unit of Haematology and Research Unit of Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark.
Insights
Detecting clonal B cells in diffuse large B cell lymphoma (DLBCL) is possible using cell-free DNA (cfDNA) from blood plasma. This method is superior to traditional tissue biopsies for identifying neoplastic cells.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Diffuse large B cell lymphoma (DLBCL) is a prevalent and heterogeneous lymphoid malignancy.
- While curable with chemo-immunotherapy in many cases, DLBCL diagnosis relies on invasive histopathology.
- Current diagnostic methods for DLBCL can be invasive and require tissue samples.
Purpose of the Study:
- To evaluate the utility of cell-free DNA (cfDNA) in blood plasma for detecting clonal B cells in DLBCL patients.
- To compare the sensitivity of cfDNA analysis with traditional cellular DNA analysis from various sources.
- To establish blood plasma as a viable source for non-invasive DLBCL detection.
Main Methods:
- Next-generation sequencing (NGS) was employed to analyze rearranged immunoglobulin heavy chain genes in cfDNA.
- Blood plasma cfDNA, lymphoma tissue DNA, and bone marrow/blood mononuclear cell DNA were analyzed from 15 DLBCL patients.
- Clonal B cell sequences and their frequencies were quantified in all sample types.
Main Results:
- Identical clonal B cell rearrangements were detected in both blood plasma cfDNA and excised lymphoma tissue.
- Plasma cfDNA demonstrated superior sensitivity in detecting clonal rearrangements compared to cellular DNA from blood or bone marrow.
- NGS analysis of cfDNA provides a sensitive method for identifying DLBCL-specific genetic markers.
Conclusions:
- Blood plasma cfDNA is a reliable and accessible source for detecting neoplastic cells in DLBCL.
- This non-invasive approach offers a promising alternative to traditional tissue biopsies for DLBCL diagnosis and monitoring.
- Further research can explore the clinical application of cfDNA in DLBCL management.
Introduction:
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in the western world. It is highly heterogeneous with a variable clinical course, but curable with chemo-immunotherapy in up to 70% of all cases. The lymphoma presents in lymph nodes and/or extranodal lymphoid tissue, and the diagnosis is based on invasive procedures for histopathologic evaluation.
Methods:
In this technical study, we evaluated cell-free DNA (cfDNA) from blood plasma to detect clonal B cells in patients with DLBCL using rearranged immunoglobulin heavy chain gene as targets by next-generation sequencing. Clonal B cell sequences and frequencies were determined from blood plasma cfDNA and cellular DNA from matched excised lymphoma tissues and mononuclear cells isolated from diagnostic bone marrow and blood samples from 15 patients.
Results:
We showed that identical clonal rearrangements could be detected in blood plasma and excised lymphoma tissue and that plasma cfDNA was superior in detecting clonal rearrangements compared to blood or bone marrow-derived cellular DNA.
Conclusion:
These findings consolidate the role of blood plasma as a reliable and easily accessible source for detecting neoplastic cells in DLBCL.
