Abstract B29: Inactivation of suppressor of fused alone is not sufficient to cause medulloblastoma
Bibliographic record
Abstract
Abstract Hedgehog (Hh) signaling is essential for embryonic development and adult homeostasis. Aberrant pathway activity can result in various developmental disorders and tumors. The Hh receptor Patched (PTCH1) is a negative regulator of the pathway and acts as a tumor suppressor. We and others have shown that suppressor of fused (SU(FU)) and KIF7 are two major negative regulators of the pathway downstream of PTCH1. Medulloblastoma (MB), the most common and aggressive pediatric brain tumor arising in the cerebellum, involves deregulation of Hh signaling. Similar to those observed in patients with PTCH1 mutations, Ptc1+/− mice spontaneously develop MB. In Ptc1+/− mice, the incidence of MB increases upon exposure to DNA damaging agents or a compounded loss of other tumor suppressor genes, such as p53. SU(FU) mutations have been found in MB, suggesting that SU(FU) is also a tumor suppressor in the cerebellum. However, we found that Su(fu)+/− mice do not develop any spontaneous MB, and that upon neonatal exposure to X-ray irradiation as well as a chemical carcinogen, these mice do not form any tumors. To examine the potential tumor suppressor function of Su(fu) in the brain, we performed conditional deletion of Su(fu) in neural progenitors. In mice, deletion of Su(fu) in neural progenitors using the Nestin-Cre line resulted in a disorganized cerebellum and motor defects. Unexpectedly, unlike Nestin-Cre;Ptc1f/- mice which developed MB, MB formation was not observed in Nestin-Cre;Su(fu)f/- mice. In contrast, similar to those reported previously, 100% of Su(fu)+/−;p53−/− mice developed MB between 2.5–4 months of age. Molecular analysis of primary tumor cell lines from these MBs revealed a loss of the wild type Su(fu) allele in the tumors. Together, these observations indicate that loss of Su(fu) alone is not sufficient for transformation into MB and suggest that other molecules, such as Kif7, may possess compensatory functions in the suppression of the tumor phenotype. Currently, we are examining the effects of Kif7 inactivation alone and in conjunction with Su(fu) inactivation on MB formation. Citation Information: Cancer Res 2009;69(23 Suppl):B29.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 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".