Abstract 3041: Focal amplification of chromosome 9p13 is associated with progression risk and activation of multiple oncogenes in oral precancers
Bibliographic record
Abstract
Abstract Oral squamous cell carcinoma, the most common form of head and neck cancer, has a dismal five year survival rate of ∼50%. This is largely due to the late stage of diagnosis and high rates of recurrence. A better understanding of the mechanisms driving early oral tumorigenesis is an essential first step towards increasing survival rates, which have not improved in decades. Specifically, by characterizing genetic alterations in early oral premalignant lesions (OPLs), we will better understand mechanisms of disease progression and discover targets for timely therapeutic intervention that could ultimately improve oral cancer outcomes. Methods: Whole genome DNA copy number profiling was undertaken on a rare panel of OPLs with extensive longitudinal data (including known progression status for invasive disease). Recurring alterations were characterized and gene lists were refined using independent tumor-associated gene expression datasets. The functional significance of remaining gene candidates was then assessed using lentiviral shRNA and expression vectors in cell model systems. Results: Analysis of genomic data from OPLs identified four focal recurrent alterations. Three of these alterations were associated with previously identified oncogenes: cMYC, EGFR, and KRAS. The fourth was a novel 2.04 Mbp amplification at chromosome 9p13. Based on our results and publicly available gene expression data, four candidate genes were found in this region: VCP, DCTN3, STOML2, and TLN1. Independent manipulation of each of these genes in cell models revealed changes in oncogenicity (based on changes in rate of proliferation and the degree of anchorage independence), suggesting a critical role in malignant processes associated with cancer progression. Conclusion: We have shown that a recurring, focal 9p13 amplicon in OPLs is associated with progression to invasive oral cancer. Further, our data indicate that this region spans multiple genes with oncogenic potential. Taken together, our results suggest that a single amplification event may dysregulate multiple genes that drive progression to invasive oral cancer. 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 3041. doi:10.1158/1538-7445.AM2011-3041
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.004 | 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".