Genetic Abnormalities Involved in the Development and Progression of Follicular Lymphoma.
Bibliographic record
Abstract
Abstract Background: Follicular lymphoma (FL) is the most common indolent B-cell lymphoma and remains incurable by current therapeutic approaches. Clinical course is variable, and transformation into an aggressive lymphoma (t-FL) with marked worsening of prognosis occurs in 20–60% of patients. While Bcl2 gene translocation is a critical initiating event in the majority of FL cases, evidence indicates it is not sufficient for the development of a FL. Characterization of the genetic alterations subsequent to Bcl2 translocation will lend insight into the oncogenic pathways that contribute to FL pathogenesis and the molecular mechanisms underlying variability in clinical course. Methods: To define recurrent genomic copy number alterations (CNA) in FL, we performed high resolution array comparative genomic hybridization (aCGH) using the Affymetrix 500K SNP array platform. aCGH data were generated on a series of 112 FL cases with available gene expression profiling (GEP) and clinical information. Gene expression data were correlated with copy number data using the Gene Expression and Dosage Integrator (GEDI) algorithm developed at the NCI. Results: Selecting for abnormalities occurring in >10% of cases, the minimal common region (MCR) for 38 losses and 31 gains were defined. Novel common regions included gains on 15q11, 16p11, 5p14 and 19q13, and losses on 3q29, and 16p13. The MCR identified by aCGH were also compared with our existing cytogenetic data on 360 FL cases. MCR residing within the most frequent cytogenetic imbalances (>5%) were selected for analysis at the gene level to further refine these regions. These include gains on 1q21, 2p16, 7q11, 8q24, 12q13, 17q21, 18q21, 21q11, and X, and losses on 1p36, 6q, 10q, 13q34, and 17p13. Recurrent amplifications were detected for the 2p16, 15q11, and 17q21 MCR, while frequent uniparental disomy (UPD) was found to overlap the region of loss on 1p36. Recurrent UPD was also noted on 6p, 12q, 15q and 16p. For the majority of selected MCR, global expression of the genes residing in the MCR demonstrated an association with copy number status. Within these abnormalities, individual genes showing significant correlation with copy number were also identified. Conclusion: The combination of high resolution aCGH and GEP facilitated the identification of functionally relevant genes within the chromosomal abnormalities in FL. Delineation of these molecular targets will provide insight into the oncogenic pathways that contribute to FL disease pathogenesis and may provide novel therapeutic targets.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".