<scp> <i>GREB1</i> </scp> ‐rearranged uterine tumour shares a common <scp>DNA</scp> methylation signature with <scp> <i>ESR1</i> </scp> ‐rearranged <scp>UTROSCT</scp>
Bibliographic record
Abstract
BACKGROUND AND OBJECTIVES: GREB1-rearranged uterine tumours encompass a group of uterine mesenchymal tumours with varied histologic appearances. The fusion partners to GREB1 include NCOA1-3, SS18 and NR4A3. Given that some GREB1-rearranged uterine tumours exhibit histologic features of uterine tumours resembling ovarian sex cord tumour (UTROSCT), there is a general belief that GREB1-rearranged uterine mesenchymal tumours are part of the UTROSCT family. METHODS: In this study, we applied global DNA methylation and copy number analyses to a series of 10 GREB1-rearranged uterine tumours and 21 classic UTROSCTs (7 of which were molecularly confirmed to harbour ESR1::NCOA2/3 fusions). RESULTS: We found that GREB1-rearranged uterine tumors show an overlap in their global methylation profiles with UTROSCT, including ESR1::NCOA2/3 positive cases. Together, these tumours form a DNA methylation cluster separate from uterine smooth muscle tumours (leiomyomas and leiomyosarcomas), endometrial stromal sarcomas (low-grade and high-grade), embryonal rhabdomyosarcoma and SMARCA4-deficient uterine sarcomas. However, despite their epigenetic similarity, there were two notable differences. First, GREB1-rearranged uterine tumours as a group displayed a greater degree of genomic complexity with more extensive copy number alterations than conventional UTROSCTs, including those harbouring ESR1::NCOA2/3. Second, GREB1-rearranged uterine tumours frequently lacked overt sex cord morphology: while all 7 ESR1::NCOA2/3 UTROSCTs demonstrated corded, nested, trabecular and/or tubular/sertoliform patterns, only 1 GREB1-rearranged uterine tumour displayed a prominent trabecular pattern, with the remaining cases showing exclusively or predominantly diffuse/solid growth. CONCLUSIONS: Overall, our findings confirm that GREB1-rearranged uterine tumours are part of the UTROSCT spectrum, though they frequently exhibit a more diffuse growth pattern and a higher degree of genomic instability.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| 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; both teacher heads agree on what is shown here.
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".