Methylation of adenomatous polyposis coli in endometrial cancer occurs more frequently in tumors with microsatellite instability phenotype.
Bibliographic record
Abstract
Differential methylation is an important epigenetic control mechanism, which has been implicated in the development of a variety of cancers. Methylation of promoter regions of normally unmethylated tumor suppressor genes leads to transcriptional inactivation and ultimately to tumor formation. We hypothesized that epigenetic inactivation of adenomatous polyposis coli (APC), a key player in the suppressor pathway, may contribute to the development of endometrial cancer. We investigated APC methylation in endometrial adenocarcinoma specimens obtained from a series of patients (n = 114) and compared methylation profiles with microsatellite instability (MSI+) status. DNA microdissected from formalin-fixed, paraffin-embedded matched normal and tumor specimens, and a subset of associated endometrial hyperplasia was subjected to methylation-specific PCR of the APC promoter 1A region. Tumor-specific hypermethylation of APC with corresponding unmethylated normal endometrial tissue occurred in 43% (17 of 40) of MSI+ cases (P = 0.0007) and 16% (12 of 74) of microsatellite stable cases (P = 0.04). Interestingly, tumor tissue was unmethylated with normal tissue displaying APC methylation in 4% (5 of 114, 2MSI+ and 3 microsatellite stable) of cases. Endometrial cell lines AN3CA, RL95-2, and HEC-1B all displayed exclusive methylation of promoter 1A, and treatment of the AN3CA cell line with the demethylating agent 5-aza-2'-deoxycytidine exhibited re-expression of APC as confirmed by RT-PCR analysis. Our results demonstrate APC methylation in endometrial cancer for the first time and show that APC hypermethylation occurs at an increased frequency in MSI+ endometrial tumors (P = 0.01).
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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) | 0.002 | 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".