Functional Genomics Identifies Drivers of Medulloblastoma Dissemination
Bibliographic record
Abstract
Medulloblastomas are malignant brain tumors that arise in the cerebellum in children and disseminate via the cerebrospinal fluid to the leptomeningeal spaces of the brain and spinal cord. Challenged by the poor prognosis for patients with metastatic dissemination, pediatric oncologists have developed aggressive treatment protocols, combining surgery, craniospinal radiation, and high-dose chemotherapy, that often cause disabling neurotoxic effects in long-term survivors. Insights into the genetic control of medulloblastoma dissemination have come from transposon insertion mutagenesis studies. Mobilizing the Sleeping Beauty transposon in cerebellar neural progenitor cells caused widespread dissemination of typically nonmetastatic medulloblastomas in Patched(+/-) mice, in which Shh signaling is hyperactive. Candidate metastasis genes were identified by sequencing the insertion sites and then mapping these sequences back to the mouse genome. To determine whether genes located at transposon insertion sites directly caused medulloblastomas to disseminate, we overexpressed candidate genes in Nestin(+) neural progenitors in the cerebella of mice by retroviral transfer in combination with Shh. We show here that ectopic expression of Eras, Lhx1, Ccrk, and Akt shifted the in vivo growth characteristics of Shh-induced medulloblastomas from a localized pattern to a disseminated pattern in which tumor cells seeded the leptomeningeal spaces of the brain and spinal cord.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".