PDTM-22. A C19MC-LIN28A-MYCN ONCOGENIC CIRCUIT DRIVEN BY HIJACKED SUPER-ENHANCERS IS A DISTINCT THERAPEUTIC VULNERABILITY IN ETMRS – A LETHAL BRAIN TUMOR
Bibliographic record
Abstract
Abstract Embryonal tumors with multi-layered rosettes (ETMR) are aggressive brain cancers with characteristic C19MC oncomiR amplification and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a potent C19MC-LIN28A-MYCN circuitry driven by multiple regulatory loops and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. C19MC and LIN28A targets respectively converge on critical cell cycle tumor suppressors and neo-embryonic DNMT3A/B isoforms. We identify a MYCN driven, core transcriptional network, conserved in early neural stem cells, that is potently abrogated by treatment with bromodomain inhibitor JQ1, leading to ETMR cell death. Our collective data suggest C19MC oncomiRs drive a malignant primitive cell state in ETMRs via entrapment of an early neural lineage network, which represents a critical therapeutic vulnerability for this recalcitrant disease.
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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 | 0.000 | 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".