CSIG-12. EXPLORING THE FUNCTIONAL RELATIONSHIP BETWEEN CAPICUA (CIC) AND ATAXIN-1-LIKE (ATXN1L) IN GLIOMA
Bibliographic record
Abstract
Oligodendroglioma (ODG), a molecularly defined subtype of glioma, is a treatment responsive, slow growing tumour strongly associated with IDH mutation and 1p19q co-deletion. Mutations in CIC, located on chromosome 19q, have been found in up to 70% of IDH mutated, 1p19q co-deleted ODGs; suggesting that loss or altered function of CIC may be crucially associated with ODG’s unique biology. CIC and ATXN1L have previously been implicated in neurodegeneration, however, this interaction has not been studied in cancer. CIC and ATXN1L interaction was confirmed using immunoprecipitation and immunofluorescence in multiple cell lines. CIC and ATXN1L knockout (KO) cell lines were generated using CRISPR/Cas9 followed by gene expression profiling using Affymetrix microarray. Differential gene expression analysis was also performed on patient lower grade glioma (LGG) RNAseq data publicly available through TCGA. Functional biology experiments to further characterize CIC-ATXN1L interaction were also performed using KO cell systems. Immunoprecipitation and immunofluorescence confirmed CIC and ATXN1L interaction within the cell nucleus of multiple cell lines. Differential expression (DE) analysis of CIC KO, ATXN1L KO and TCGA LGG cohort converged on activation of the MAPK pathway and dysregulation of central nervous system development; with significant overlap in differentially expressed genes (n=110). Furthermore, experiments using our KO cell systems suggest a functionally reciprocal relationship between CIC and ATXN1L and regulation of their respective pathways. CIC and ATXN1L form a functionally reciprocal relationship where loss of one partner leads to dysregulation of both partners. Although CIC mutations are predominant in ODGs, the CIC-ATXN1L axis may be exploited in other gliomas and cancers which rely on maintaining MAPK signaling such as EGFR amplified glioblastoma and may be a target for future prognostics and therapeutics.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.011 | 0.006 |
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".