Epigenetic silencing of the <i>MGMT</i> gene in cancer
Bibliographic record
Abstract
Silencing of the O6-methylguanine-DNA methyltransferase (MGMT) gene, a key to DNA repair, plays a critical role in the development of cancer. The gene product, functioning normally, removes a methyl group from mutagenic O6-methylguanine, which is produced by alkylating agents and can make a mismatched pair with thymine, leading to transition mutation through DNA replication. MGMT is epigenetically silenced in various human tumors. It is well known that DNA hypermethylation at the promoter CpG island plays a pivotal role in the epigenetic silencing of tumor suppressor genes. MGMT silencing, however, occurs without DNA hypermethylation in some cancer cells. Dimethylation of histone H3 lysine 9 and binding of methyl-CpG binding proteins are common and essential in MGMT-silenced cells. Silencing of MGMT has been shown to be a poor prognostic factor but a good predictive marker for chemotherapy when alkylating agents are used. In this review, we describe recent advances in understanding the silencing of MGMT and its role in carcinogenesis; epigenetic mechanisms; and clinical implications.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".