Abstract 2415: The role of GTSF1 as a regulator of retrotransposons and its impact on carcinogenesis
Bibliographic record
Abstract
Abstract Hypomethylation of repetitive sequences is a common feature reported in cancer, particularly of retrotransposon elements. Retrotransposon elements can be deleterious due to their potential as insertional mutagens, so cells have deployed several control mechanisms to silence them through methylation of DNA. These methylation pathways are different between somatic and germline cells. In germline cells, the piRNA pathway is the main process responsible for silencing the retrotransposon LINE-1. GTSF1 is germline cell specific and an important part of this pathway. Along with PIWI proteins in the piRNA pathway, GTSF1 processes small RNA molecules and identifies active retrotransposons, recruiting the DNA methylation machinery to those sites. Aberrant expression of GTSF1 has been reported in cancer, particularly on lymphomas. We performed a Bayesian Analysis and Markov Chain Monte Carlo Method with GTSF1 levels of expression reported on The Cancer Genome Atlas (TCGA), which confirmed high levels of mRNA in lymphomas. Nonetheless, the role of GTSF1 in retrotransposon control in cancer and in carcinogenesis remains unknown. To address this issue, we have performed shRNA mediated knockdown in head and neck squamous cell carcinoma and cutaneous T-cell lymphoma cell lines, and we have overexpressed the cDNA of GTSF1 in immortalized keratinocytes. We evaluated the impact of the knockdown and overexpression on cell biology, retrotransposons, and genomic instability. Overall, GTSF1 expression seems to affect LINE-1 retrotransposon protein expression and function. Also, we are assessing the impact on genomic instability and methylation profiles. The aberrant expression of this gene poses an excellent clinical opportunity for targeted therapy development. Its germline cell restricted expression will potentially result in less secondary effects than current available therapies. Citation Format: Amelia Martínez Villarreal, Jennifer Gantchev, Ivan Litvinov. The role of GTSF1 as a regulator of retrotransposons and its impact on carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2415.
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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) | 0.003 | 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 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".