Aberrant Immunoglobulin Class Switch Recombination and Switch Translocations in Activated B Cell-Like Diffuse Large B-Cell Lymphoma.
Bibliographic record
Abstract
Abstract To elucidate the mechanisms underlying chromosomal translocations in diffuse large B-cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used a Southern blot assay to detect legitimate and illegitimate CSR events in 92 primary tumor samples of either the activated B-cell-like (ABC; n = 50), germinal center B cell-like (GCB; n =31), and primary mediastinal B cell lymphoma (PMBL; n = 11) subgroups of DLBCL. We could clearly distinguish ABC DLBCL from GCB and PMBL by the phenotype shown in these experiments. The frequency of legitimate CSR was significantly lower in ABC DLBCL compared to GCB DLBCL and PMBL (30% vs. 58% vs. 64%; p = 0.012 and p = 0.035 respectively). In contrast, illegitimate switch recombination events were more frequent in ABC than in GCB (56% vs. 32%; p = 0.037). Similarly, ABC DLBCL had a higher frequency of internal deletions within the switch μ region compared to GCB DLBCL and PMBL (48% vs. 13% vs. 0%; p = 0.0012 and p = 0.003, respectively). ABC DLBCLs also had frequent deletions within Sγ (66%) and Sα (26%). Sequence analysis revealed ongoing Sμ deletions within ABC DLBCL tumor clones, with 4–19 separate deletions occurring per case. In addition, Sμ deletions were accompanied by ongoing segmental duplications and apparent AID-dependent somatic mutations in Sμ, consistent with failed attempts at AID-mediated CSR. Unexpectedly, short fragments derived from multiple chromosomes were interspersed within the deleted Sμ regions. Furthermore, aberrant switch recombination was responsible for translocations in ABC DLBCLs involving the known oncogenes BCL6 and MYC. In addition, we were able to identify a novel translocation involving the switch γ3 region and the gene encoding the B-cell transcription factor SPIB in the ABC cell line OCI-Ly3. These findings suggest that ABC DLBCLs have abnormalities in the regulation of CSR that predispose to chromosomal translocations.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".