Chromobox 4 (CBX4) Is a Novel Interactor of SS18::SSX in Synovial Sarcoma
Bibliographic record
Abstract
Synovial sarcoma is an aggressive cancer generally affecting adolescents and young adults and is characterized by high rates of recurrence and metastasis. It is primarily driven by the fusion oncoprotein SS18::SSX, the product of a pathognomonic chromosomal translocation t(X;18), which facilitates widespread epigenetic dysregulation through interactions with complexes, such as the BRG1/BRM-associated factor complex and polycomb repressive complexes. Previous attempts to perform mass spectrometry (MS) of the SS18::SSX interactome have been limited by the lack of an antibody to detect the endogenous protein, hence relying on single-cell lines with exogenous tags. We previously used a monoclonal antibody, which specifically detects SS18::SSX containing the canonical fusion junction (seen in 95% of cases) and established its utility in several applications. Using that antibody, MS analysis revealed that the SS18::SSX protein undergoes alternative splicing of exon 8 in SS18. We next performed immunoprecipitation MS of SS18::SSX in 6 immortalized human synovial sarcoma cell lines and identified the canonical polycomb repressive complex member chromobox 4 (CBX4), as a novel interactor of the oncoprotein. Immunohistochemical staining of several epigenetic factors on a human synovial sarcoma tissue microarray showed an association of synovial sarcoma samples with higher CBX4 expression. Last, an analysis of CBX4 expression across 337 samples from 12 sarcoma subtypes, carcinomas, and normal tissue demonstrates higher expression in synovial sarcoma samples compared with other tissue types. These results highlight a crucial approach in identifying important partners of SS18::SSX in synovial sarcoma to establish new biological pathways that contribute to the disease.
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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 | 0.001 |
| 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".