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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
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Clonal relationships in recurrent B-cell lymphomas
Seung Eun Lee1, So Young Kang2, Hae Yong Yoo3
1Department of Pathology, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Korea.
Oncotarget
|February 6, 2016
Summary
Relapse in B-cell lymphomas can originate from an unrelated clone, though uncommon. Sequencing immunoglobulin (Ig) genes, not just PCR fragment size, is crucial for determining clonal relationships between primary and relapsed tumors.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Immunoglobulin (Ig) gene rearrangements are typically stable during neoplastic cell clonal expansion.
- Understanding clonal relationships in lymphoma relapse is critical for accurate diagnosis and treatment.
Purpose of the Study:
- To investigate clonal relationships between primary B-cell lymphomas and their relapsed counterparts.
- To evaluate the reliability of different molecular methods for assessing clonal origin in lymphoma relapse.
Main Methods:
- Analysis of Ig gene rearrangements in 27 paired primary and relapsed lymphoma tissues using BIOMED-2 multiplex PCR.
- Cloning and sequencing of amplified Ig genes in 17 patients to confirm VDJ rearrangements.
- Comparison of fragment lengths and DNA sequences to establish clonal identity.
Main Results:
- All 27 cases showed monoclonal Ig gene rearrangements by PCR.
- Fragment length analysis was discordant in 70% of cases, while sequencing confirmed identical VDJ rearrangements in 77% of cases with differing fragment lengths.
- Unrelated relapses occurred in a minority of cases, were associated with longer disease-free intervals, and tended towards poorer outcomes.
Conclusions:
- Relapse from an unrelated clone is an uncommon but significant event in B-cell lymphomas.
- Sequencing of Ig gene rearrangements provides a more definitive assessment of clonal relationships than PCR fragment size alone.
- Accurate determination of clonal origin is essential for understanding lymphoma behavior and patient outcomes.
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