Abstract 240: Amplification status of GAS41 and MDM2 in lung adenocarcinomas
Bibliographic record
Abstract
Abstract Background: Lung cancer is the leading cause of cancer death worldwide. High mortality rates are attributed to inefficient therapeutic strategies and a lack of screening for early detection. Identification of genes involved in lung cancer development may yield new molecular targets for diagnosis and treatment. It is well documented that the lung cancer genome harbors genetic alterations. We hypothesize that novel oncogenes can be discovered through characterization of chromosomal regions frequently amplified in lung adenocarcinoma. Methods: A panel of 169 matched lung adenocarcinoma tumors was studied. Genetic profiles describing copy number alterations and gene expression were generated by whole genome array comparative genomic hybridization and Affymetrix platforms respectively, and visualized using SIGMA2 software. Regions of DNA amplifications were identified using the GISTIC algorithm and integrated with expression data to determine if amplification is associated with overexpression in tumors relative to matched normal tissue. An MTT assay was used to investigate the effect of cell proliferation after shRNA-mediated knockdown in a cell line with DNA amplification. Survival analysis using multiple independent data sets was also performed to assess the clinical significance of gene amplification and overexpression. Results: A preliminary genome wide screen revealed Glioma Amplified Sequence 41 (GAS41) at 12q13-15 as frequently amplified and overexpressed in lung cancer. GAS41 suppresses cell cycle checkpoint genes p21 and p14, causing indirect repression of the p53 tumor suppressor, promoting tumorigenesis. Amplification of this gene has been reported in the earliest stages of glioma and astrocytoma. GAS41 is amplified in 16.57% of the lung adenocarcinoma tumors (28 of 169) analyzed and consistently overexpressed. Knockdown of GAS41 slowed cell proliferation, consistent with its biological function. Additionally, patients expressing high levels of GAS41 mRNA showed markedly poorer outcomes than those with lower expression. Conclusions: Our data highlights the tumorigenic potential of GAS41, suggesting that amplification of this gene may be a critical alteration in lung cancer. GAS41 amplification and subsequent activation may represent a novel mechanism driving lung tumorigenesis. The association of GAS41 expression with survival and its demonstrated effect on cell proliferation make it a potential prognostic marker and therapeutic target in lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 240.
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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 | 0.000 |
| 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) | 0.002 | 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".