Chromosomal alterations in oligodendroglial tumors over multiple surgeries: Is progression associated with change in 1p/19q status?
Bibliographic record
Abstract
10577 Background: There is morphologic and genotypic heterogeneity of oligodendroglial neoplasms. Tumors with loss of heterozygosity (LOH) of 1p and/or 19q are associated with increased chemo-sensitivity and survival. Despite treatment, rates of recurrence and malignant transformation are high. The pathogenesis of treatment-resistance is unknown. We aim to determine if tumour progression is associated with a proliferation of clonagens with retention of heterozygosity (ROH) of 1p, or if progressing tumours remain 1p/19q LOH. Methods: Between 1/1/2001 and 7/31/2006, 24 patients with oligodendroglial neoplasms, and possessing serial biopsies taken at diagnosis and at progression, were identified. Using PCR amplification of multiple microsatellite markers, a total of 53 tumour specimens were available for LOH analysis of 1p and 19q; 40 were also tested for 9p and 10q. Results: At diagnosis, the median age was 34 (24–66) years and 14 were male. Using the WHO criteria, 19 tumors were Grade II oligodendrogliomas or oligoastrocytomas, and 5 were high grade. The most common genomic status was 19q LOH (88%); 54% had 1p LOH. Of the 13 primary biopsies with 1p LOH, 11 had 19q LOH, 1 had 19q ROH, and 1 was 19q non-informative. A further 2 primaries were mixed 1p LOH/ROH, and 9 were 1p ROH. At progression, 10 of 11 patients with 1p/19q LOH had persistent co-deletion. The patient with 1p LOH and 19q ROH at diagnosis, had 1p/19q LOH at progression. Of the mixed 1p primaries, 1 was 1p ROH, and the other remained mixed LOH/ROH at progression. 8 of 9 primaries with 1p ROH remained 1p ROH. There was also little heterogeneity of 9p and 10q between primary and progressive tumours. Using Kaplain-Meier analysis, mean overall survival (OS) for the group was 102 (95% CI: 77–127) months. Mean progression-free survival was 52 (95% CI: 33–72) months. OS was not statistically significant between patients with 1p LOH and 1p ROH primary tumours. Conclusions: 91% of repeat biopsies of oligodendroglial tumors, demonstrated persistent 1p/19q LOH. Therefore, progression of 1p/19q LOH primary tumours is not due to a proliferating sub-group of chemo-resistant, 1p ROH clonagens. We propose that additional mutations contribute to this aggressive phenotype. No significant financial relationships to disclose.
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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 | 0.001 |
| 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".