Replication Timing Aberration of KIF14 and MDM4/PI3KC2β Alleles and Aneuploidy as Markers of Chromosomal Instability and Poor Treatment Response in Ewing Family Tumor Patients
Bibliographic record
Abstract
Abstract Replication timing of allelic gene pairs is strictly regulated according to expression, genome stability, and epigenetic changes, and tumorigenesis may be associated with changes in the allelic replication in various tumors. Our aim was to determine whether such alterations had a prognostic value in Ewing's family tumor (EFT) patients. The KIF14 and MDM4/PI3KC2β and the centromeric satellite sequence of chromosomes 8 and 12 were used for replication timing assessments. Aneuploidy was assessed by enumerating the copy numbers of chromosomes 8 and 12. Replication timing and aneuploidy were detected cytogenetically using multicolors fluorescence in situ hybridization assay applied in 135 EFT. Patients with trisomy 8 presented an association with an asynchronous replication pattern (SD) of MDM4/PI3KC2β genes (p = 0.013). Trisomy 12 was associated with a synchronous pattern (DD) of KIF14 probe signals (p = 0.04). The DD synchronous replication pattern of KIF14 showed a correlation with age (p < 0.0001), and the SS synchronous replication pattern of the same locus showed a correlation with lung metastatic (p = 0.012). The subgroup of patients presenting with multiplet signals of MDM4/PI3KC2β showed an association with treatment response (p = 0.045) and age (p = 0.033). Replication pattern of KIF14 may, significantly, be associated with chromosomal instability as MDM4/PI3KC2β may be a considerably new marker of poor treatment response in EFT patients.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".