A novel brain tumour model in zebrafish reveals the role of YAP activation in MAPK/PI3K induced malignant growth
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Bibliographic record
Abstract
Somatic mutations activating MAPK/PI3K signalling play a pivotal role in both tumours and brain developmental disorders. We developed a zebrafish model of brain tumour based on somatic expression of oncogenes that activate MAPK/PI3K signalling in neural progenitor cells. HRASV12 was the most effective in inducing both heterotopia and invasive tumours. Tumours, but not heterotopias, require persistent activation of phospho‑(p)ERK and express a gene signature similar to the mesenchymal glioblastoma subtype, with a strong YAP component. Application of a 8-gene signature to human brain tumours establishes that YAP activation distinguishes between mesenchymal glioblastoma and low grade glioma in a wide TCGA sample set including gliomas and glioblastomas (GBMs). This suggests that the activation of YAP may be an important event in brain tumour development, promoting malignant versus benign brain lesions. Indeed, co-expression of dominant active YAP (YAPS5A) and HRASV12 abolishes the development of heterotopias and leads to the sole development of aggressive tumours. Thus, we have developed a model proving that neurodevelopmental disorders and brain tumours may originate from the same somatic mutations activating oncogenes and established that YAP activation is a hallmark of malignant brain tumours.
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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 | 0.001 | 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) | 0.000 | 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 it