PM-16 * AN ANIMAL MODEL OF 17p DELETION IN MEDULLOBLASTOMA
Bibliographic record
Abstract
INTRODUCTION: Medulloblastoma is the most frequent malignant pediatric brain tumor with an incidence of 0.5-0.8/100,000 children. Up to 40% of tumors have chromosome 17p deletions and 17q duplications, usually in the context of isochromosome 17q (i17q). The high frequency of i17q in medulloblastoma is hypothesized to be secondary to a role in tumor initiation and progression. To test this hypothesis we have chromosome engineered ‘17p’ deletions and ‘17q’duplications in the syntenic region of mouse chromosome 11 to evaluate the role of chromosome 17 aberrations in medulloblastoma. METHOD: The Mutagenic Insertion and Chromosome Engineering Resource (MICER) was used to chromosome engineer ‘17p’ deletions and ‘17q’ duplications. loxP sites were sequentially targeted to sites flanking the syntenic 17p or 17q region of mouse chromosome 11. Cre-recombinase deleted or duplicated the chromosome 17 target regions in mouse ES cells and recombinant clones were isolated with HAT selection. Florescent In-situ Hybridization confirmed the 18 megabase deletion of ‘17p’ and the 45 megabase duplication of 17q from mouse ES cells. Mice with Cre inducible floxed (Cis) alleles or constitutive deletion/duplication (Trans) alleles were generated. RESULTS: Chimeric founder mice with constitutive deletion/duplication (Trans) alleles were generated from mouse ES cells for both‘17p’ and ‘17q’. Offspring inherited either the desired ‘17p’ deletion allele or a ‘17p’ duplication allele. However, experimentally only ‘17p’ duplication pups were born, indicating the constitutive ‘17p’ deletion and ‘17q’ deletion/duplication alleles are likely embryonic lethal. Conditional 17p-Cis deletion mice have been bred to Nestin-cre/Ptc + /−, these mice develop medulloblastoma harboring the 18 Mbp chromosome ‘17p’ equivalent deletion in 15% of tumours. CONCLUSION: Herein we have generated a sporadic and faithful murine model of the most common cytogenetic aberration present in human medulloblastoma. This model will serve as an invaluable tool for further biological discovery and therapeutic modeling of most cases of high risk medulloblastoma.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.009 | 0.004 |
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".