Germline analysis of thymidine/guanidine polymorphism at position 309 of the Mdm2 promoter in malignant melanoma patients
Bibliographic record
Abstract
p53 is a major tumor suppressor gene, frequently mutated in human cancer, but rarely mutated in malignant melanoma (MM). Mdm2, the major negative regulator of p53, is overexpressed in 50-60% of MM patients, by an unknown mechanism. Single nucleotide polymorphism at position 309 of the Mdm2 promoter correlates with increased Mdm2 levels and reduced p53 activation. We speculated that guanine at position 309 (G309) of the Mdm2 promoter might be a cause of Mdm2 overexpression in MM patients, and associated with increased risk of MM. We aimed to estimate the prevalence of G309 in MM patients. Genomic DNA was collected from a cohort of 28 MM patients of various clinical stages. The relevant DNA stretch was sequenced and thymidine/guanidine polymorphism at position 309 of Mdm2 promoter was examined. We compared the resultant frequencies with the frequencies reported in the literature for the general population. The G allele frequency in the cohort of MM patients was 0.518. This frequency is high compared with the reported frequency of 0.351 in Caucasian healthy populations (odds ratio=1.98, P=0.014). It is also higher than a G allele frequency of 0.464 reported for Ashkenazi Jewish women, although this comparison was not statistically significant (odds ratio=1.14, P=0.76). These results suggest that the single nucleotide polymorphism G309 in the Mdm2 promoter might be an important genetic predisposing factor, and possibly indicate a molecular mechanism of disease regarding MM. These results must be confirmed in a larger cohort of MM patients and controls.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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".