Exploration of the mutational landscape of cutaneous leiomyoma confirms <i>FH</i> as a driver gene and identifies targeting purine metabolism as a potential therapeutic strategy
Bibliographic record
Abstract
To comprehensively explore the mutational landscape of cutaneous leiomyoma (cLM) and identify candidate driver events, we performed a retrospective, multi-institutional, whole-exome sequencing and RNA sequencing study. We confirmed that a large proportion of patients with cLM have germline FH variants and additionally showed that somatic alteration of FH also drives cLM, with biallelic inactivation of FH being a frequent event. Treatment of Fh1-proficient and -deficient cell lines with the purine antagonist and chemotherapeutic agent, mercaptopurine, significantly decreased growth/colony formation; however, the addition of nucleosides was able to rescue only the Fh1-proficient cells, suggesting that purine metabolism is a targetable vulnerability for FH-deficient cLMs.
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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".