Abstract 2476: A novel NUT translocation partner binds to BRD4 and is necessary for the blockade of differentiation in NUT midline carcinoma
Bibliographic record
Abstract
Abstract NUT midline carcinoma (NMC) is an aggressive type of squamous cell carcinoma that typically harbors BRD4/3-NUT fusion oncogenes which encode chimeric proteins that block differentiation and maintain tumor growth. However, in 30% of cases NUT is fused to yet to be identified non-BRD gene(s). Using RNA sequencing, we identified a novel gene fused to NUT in a NMC cell line (1221), fusing a novel 5′ coding sequence to the NUT gene. Like Brd4/3, this gene encodes a protein that is also involved in epigenetic regulation, and we find that siRNA knockdown of this protein leads to differentiation of the 1221 cells as well as of three BRD4-NUT-positive NMC cell lines. We have established that the novel NUT fusion protein encoded by this translocated gene binds to BRD4. We have mapped the regions of Brd4 and of the novel fusion protein involved in complex formation and are exploring whether association of the novel protein with Brd4 is required for the blockade of differentiation in NMC. Differentiation of TC-797 cells induced by knockdown of BRD4-NUT is abrogated by enforced expression of the novel NUT-fusion gene. Together, these findings identify a novel BRD4-NUT-interacting protein whose expression is required for the maintenance of the undifferentiated state in NMC, and when fused to NUT, is oncogenic and can recapitulate the function of BRD4-NUT to block differentiation. Citation Format: Erica Walsh, Simone Kuhnle, Shaila Rahman, Madeleine Lemieux, Peter Howley, Christopher French. A novel NUT translocation partner binds to BRD4 and is necessary for the blockade of differentiation in NUT midline carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2476. doi:10.1158/1538-7445.AM2014-2476
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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 | 0.000 | 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) | 0.002 | 0.001 |
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".