Abstract 2035: Alterations in nuclear DNA organization in sporadic pediatric Papillary Thyroid Carcinoma (PTC)
Bibliographic record
Abstract
Abstract Pediatric papillary thyroid carcinoma (PTC) present a more aggressive disease than adults, with higher risk of malignancy, higher rates of metastasis, multifocality and larger tumor sizes. We described AGK-BRAF fusion in 19% of sporadic pediatric PTC, which is associated with lung metastasis and younger age (mean 10.67 y.o.). Super-resolved three-dimensional structured illumination microscopy (3D-SIM) allows the visualization of the DNA structure inside the interphase nucleus at microscopic length scales. 3D-SIM has shown that cancer cell nuclei exhibit chromatin remodeling, with increased amount of DNA-poor spaces, which indicates a disrupted pattern in the DNA and has been associated with aggressive behavior in other tumor subtypes. In order to understand the underlying causes of the aggressiveness of pediatric PTC, we here aimed to analyze, for the first time, the DNA organization from 13 pediatric PTC patients (≤18 y.o.), using super-resolved 3D-SIM technology. A granulometry-based measurement method quantified the size distribution of DNA structure (DNA packaging) and DNA-poor spaces. We compared the granulometry for: tumor vs normal tissues; AGK-BRAF fusion (positive vs negative tumors); distant metastasis (presence vs absence); multifocal vs unifocal tumors; age at diagnosis (≤ 10 y.o. vs > 10 y.o.); tumor size ( ≤ 2 cm vs > 2 cm) and extra-thyroidal (ET) extension (presence vs absence). Nuclei from tumor cells exhibited larger DNA structures (p=0.0001) and more DNA-poor spaces (p<0.0001) than normal cells. In relation to the clinicopathological features, patients that presented distant metastasis (p=0.001), multifocal tumors (p=0.002) and > 2 cm tumors (p=0.0029), exhibited more DNA-poor spaces in their nuclei. Regarding the analyses of the AGK-BRAF fusion, borderline results were observed for both DNA structure (p=0.058) and DNA-poor spaces (p=0.053). Similar results were observed in PTC cases with age ≤10 y.o. for DNA structure (p=0.068) and DNA-poor spaces (p=0.06). No significant difference was observed for ET extension. Our preliminary data corroborate with previous studies, where tumor cell nuclei present more DNA-poor spaces than normal cells; and suggest a progressive disruption and remodeling of the chromatin in malignant cells. Interestingly, tumor cells from patients with features of poor prognosis (distant metastasis, multifocality and tumor size) can exhibit a more disrupted DNA organization, which can be related to a more aggressive behavior of the tumor. Moreover, can also observe a trend to a more disrupted chromatin organization in AGK-BRAF tumors and tumors from <10 y.o. patients, which can be associated with the aggressiveness of the disease in these cases. Further analysis are needed to better understand wether AGK-BRAF fusion is associated with poor prognosis in pediatric PTC and if it could be related to a high genomic instability caused by this fusion. Citation Format: Luiza Sisdelli, Maria I. Cordioli, Fernanda Vaisman, Osmar Monte, Carlos Longui, Adriano N. Cury, Aline Rangel-Pozzo, Sabine Mai, Janete M. Cerutti. Alterations in nuclear DNA organization in sporadic pediatric Papillary Thyroid Carcinoma (PTC) [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 2035.
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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 | 0.001 | 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) | 0.001 | 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".