Diverse Oncogenic Fusions and Distinct Gene Expression Patterns Define the Genomic Landscape of Pediatric Papillary Thyroid Carcinoma
Bibliographic record
Abstract
Pediatric papillary thyroid carcinoma (PPTC) is clinically distinct from adult-onset disease. Although there are higher rates of metastasis and recurrence in PPTC, prognosis remains highly favorable. Molecular characterization of PPTC has been lacking. Historically, only 40% to 50% of childhood papillary thyroid carcinoma (PTC) were known to be driven by genomic variants common to adult PTC; oncogenic drivers in the remainder were unknown. This contrasts with approximately 90% of adult PTC driven by a discrete number of variants. In this study, 52 PPTCs underwent candidate gene testing, followed in a subset by whole-exome and transcriptome sequencing. Within these samples, candidate gene testing identified variants in 31 (60%) tumors, while exome and transcriptome sequencing identified oncogenic variants in 19 of 21 (90%) remaining tumors. The latter were enriched for oncogenic fusions, with 11 nonrecurrent fusion transcripts, including two previously undescribed fusions, STRN-RET and TG-PBF. Most fusions were associated with 3' receptor tyrosine kinase (RTK) moieties: RET, MET, ALK, and NTRK3. For advanced (distally metastatic) tumors, a driver variant was described in 91%. Gene expression analysis defined three clusters that demonstrated distinct expression of genes involved in thyroid differentiation and MAPK signaling. Among RET-CCDC6-driven tumors, gene expression in pediatric tumors was distinguishable from that in adults. Collectively, these results show that the genomic landscape of pediatric PTC is different from adult PTC. Moreover, they identify genomic drivers in 98% of PPTCs, predominantly oncogenic fusion transcripts involving RTKs, with a pronounced impact on gene expression. Notably, most advanced tumors were driven by a variant for which targeted systemic therapy exists. SIGNIFICANCE: This study highlights important distinctions between the genomes and transcriptomes of pediatric and adult papillary thyroid carcinoma, with implications for understanding the biology, diagnosis, and treatment of advanced disease in children.
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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".