Abstract 317: 1q32.1 and 16q21 genomic alterations implicate KIF14/MDM4/PIK3C2ß and CDH11 as independent prognostic markers of relapse in localized Ewing Family of Tumors
Bibliographic record
Abstract
Abstract EWS-ETS genetic fusion appears to be the initiating mechanism behind Ewing Family of Tumors (EFT) pathogenesis; however, progression of the disease is dependent on additional genetic alterations. Using the Progenetix database, we identified mainly alterations at 1q, and at 16q, as the most recurrent genetic alterations in EFT without consistency as markers of relapse. Clinic features of a large genotype cohort of 135 patients with EFT were retrospectively reviewed from A.C. Camargo hospital records. Tissue microarrays (TMA) were built for multi-color interphase fluorescent in situ hybridization (iFISH) analysis of aberrations at 1q32.1 (KIF14/MDM4/PIK3C2ß) and 16q21 (CDH11) using in-house probes. Gains were defined by the presence of more than three hybridization signals per interphase nucleus with simultaneous intact centrosome signal occurring in more than 5% of tumor nuclei. Losses were indicated by one target signal with the intact centrosome signals in more than 30% of nuclei. The frequencies of gene copy number alterations (CNA) were compared with clinical parameters and follow-ups. Statistical analyses were performed by SPSS program. A p-value of less than 0.05 was considered significant. CNA analysis showed gains at 1q32.1 in 15/128 (11.7%) cases, while abnormalities at 16q21 were seen in 24/118 (20.3%) patients, split into two groups. One group of patients, 11/118 (9.3%), showed only hemizygous deletion, whereas, the other group with 13/118 (11%) patients showed gain. A significant association between 1q32.1 gains and 16q21 losses (p=0.029) was detected, but not a significant clinical synergism when interacting at the same patient. Univariate analyses showed gains at 16q21 (p=0.029) or at 1q32.1 (p=0.005) associated with tumor relapse in the localized disease subgroup. Disease-free survival curves represented these gained regions as unfavorable outcome parameters (p<0.05) for EFT patients. The multivariate model confirmed 1q32.1 or 16q21 gains as independent prognostic markers for relapse. Hence, copy number gains at 1q32.1 and 16q21 constitute valuable markers of relapse in localized EFT. Genomic alterations of the critical genes in these chromosomal regions probably activate key downstream target genes of distinct pathways, which thus lead to an intricate molecular mechanism for EFT growth and aggressiveness. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 317. doi:10.1158/1538-7445.AM2011-317
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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) | 0.006 | 0.001 |
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".