Abstract B68: Spatial and temporal conditions for Smarcb1 deletion determines mouse AT/RT (atypical teratoid/rhabdoid tumor) subtype
Bibliographic record
Abstract
Abstract The cell(s) of origin of AT/RTs remain(s) unknown. We previously developed a mouse model consisting of tamoxifen inducible system in a Smarcb1Flox/Flox;Rosa26-CreERT2 background. We obtained two molecular subgroups of intracranial tumors, one with neuronal and the other with non-neuronal features, consistent with the diversity observed in human AT/RTs. To investigate the potential cell(s) of origin of these various AT/RTs, we first explored whether different time points of Smarcb1 inactivation correlated with anatomic location and/or molecular subgroups. We observed that the neuronal group, primarily developing from the subventricular zone and the spinal cord, was almost exclusively obtained with the earliest inactivation time points (E6-E7). In contrast, the non-neuronal group emerged upon Smarcb1 inactivation at any time point (E6-E10) and showed intracranial but extra-parenchymal/meningeal origins. High-resolution analysis of anatomic distribution of 55 human AT/RT and molecular subgroups is in progress. In order to more specifically identify the cell(s) of origin for the neuronal group, we next generated developmental stage-specific conditional knockout mice carrying Smarcb1 inactivation by restricting Cre expression with promoters characteristic for various neural stem cells/progenitors. While Smarcb1Flox/Flox;Atoh1CreERT2 showed ataxia but failed to give rise to any tumor at any embryonal time point, Smarcb1Flox/Flox;Ascl1CreERT2 did not show any phenotype. Targeting Nestin-expressing cells led to tumors with morphologic rhabdoid features; these tumors again showed molecular diversity as observed in human AT/RTs. In conclusion, we show that deletion of Smarcb1 determines mouse AT/RT subtypes depending on spatial and temporal factors. Our new mouse models not only give insight into the cell(s) of origin, but also provide interesting preclinical models of AT/RTs. Citation Format: Zhi-Yan Han, Mamy Andrianteranagna, Maria Jesus-Lobon-Iglesias, Arnault Tauziède-Espariat, Kevin Beccaria, Paul Fréneaux, Joshua J. Waterfall, Julien Masliah-Planchon, Christine Bourneix, Gaelle Pierron, Amaury Leruste, Céline Chauvin, Didier Surdez, Pascale Varlet, Christelle Dufour, Olivier Delattre, Volodia Dangouloff-Ros, Franck Bourdeaut. Spatial and temporal conditions for Smarcb1 deletion determines mouse AT/RT (atypical teratoid/rhabdoid tumor) subtype [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B68.
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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) | 0.000 | 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 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".