Abstract 1447: Investigating susceptibility to sporadic osteosarcoma by genome-wide copy number analysis
Bibliographic record
Abstract
Abstract Constitutional copy-number variants (CNVs) frequently overlap genomic regions that contain genes associated with cancer. In addition, copy number alterations (CNAs) in tumors often coincide with sites of CNVs and may arise through progression of CNVs. Osteosarcoma (OS), the most common human bone malignancy, can arise in familial or sporadic forms. While germline mutations of tumor suppressor genes have been implicated in a minority of OS cases, little is known about genetic changes that contribute to the etiology of sporadic OS. Using high-resolution SNP/CNV arrays, we observed a higher global germline CNV frequency in patients with sporadic OS compared to healthy controls. Given the early age of onset and the extensive constitutional CNVs, we hypothesize that these genomic alterations are linked to susceptibility to OS. Here we investigate whether specific constitutional CNVs are related to susceptibility to sporadic OS and whether OS tumor CNAs arise via progression of constitutional CNVs in these patients. Blood derived DNA samples from patients with sporadic OS with wild-type germline p53 sequence and gene dosage were selected for analysis on Affymetrix GW6.0 arrays with paired pre-therapy tumor biopsies. Initial results from a discovery set of samples (n=43 pairs) reveal a copy number loss at 1q43, in a region that overlaps several genes that have a role in bone formation, microtubules and cytoskeletal organization. This loss was present in 43% of the blood-derived DNA samples and 44% of the tumor-derived samples, whereas this variant was noted in only 1.2% of controls. Furthermore, the germline 1q43 deletion correlates with poor survival of the OS patients (p=0.04, Long Rank). Analysis of an independent validation set (n=32 pairs) is currently underway to confirm the initial finding and further characterize specific constitutional CNVs among sporadic OS patients. The findings of this study will open new avenues for the discovery of novel loci implicated in susceptibility to OS with potential for improved diagnostic and prognostic options as well as further insight into disease pathogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1447. doi:1538-7445.AM2012-1447
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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) | 0.003 | 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".