Loss of function of Atrx recapitulates phenotypes of alternative lengthening of telomeres in a primary mouse model of sarcoma
Bibliographic record
Abstract
<h2>Summary</h2> The development of a telomere maintenance mechanism is essential for immortalization in human cancer. While most cancers elongate their telomeres by expression of telomerase, 10–15% of human cancers utilize a pathway known as alternative lengthening of telomeres (ALT). ALT is commonly associated with loss-of-function mutations in ATRX. Here, we developed a genetically engineered primary mouse model of sarcoma in CAST/EiJ mice to investigate the extent to which telomerase deficiency and Atrx-inactivation lead to ALT induction. We observed increases in multiple ALT-associated phenotypic indicators in tumors with loss of function mutations of <i>Atrx.</i> Furthermore, we found that loss of <i>Atrx</i> leads to an increase in telomeric instability and telomere sister chromatid exchange. However, Atrx-deficient tumors did not show productive telomere length maintenance in the absence of telomerase. This primary mouse model of sarcoma could facilitate future investigations into the molecular features of ALT <i>in vivo</i>.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| 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".