Paediatric Thyroid Carcinoma: The Genetic Revolution and Its Implications for Therapy and Outcomes
Simple Summary
Abstract
1. Introduction
2. Somatic Gene Alterations in Differentiated Thyroid Carcinomas
2.1. RET
2.2. NTRK
2.3. ALK
2.4. BRAF
2.5. TERT
2.6. RAS
2.7. Pax-8/PPAR-Gamma
3. Germline P/LPV Associated with Predisposition to Thyroid Carcinomas
3.1. PTEN Hamartoma Tumour Syndrome
3.2. DICER1 Syndrome
3.3. Carney Complex Type 1
3.4. Familial Adenomatous Polyposis
3.5. Werner Syndrome
3.6. Multiple Endocrine Neoplasia Type 2
4. Germline Molecular Testing for Cancer Predisposition Syndromes
5. Molecular Testing of Thyroid Nodule FNA Samples
6. The Value of a Molecular Diagnosis Post-Operatively
7. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Diagnostic Category | ROM Mean (Range) | |
---|---|---|
I | Nondiagnostic | 14% (0–33) |
II | Benign a | 6% (0–27) |
III | Atypia of undetermined significance | 28% (11–54) |
IV | Follicular neoplasm b | 50% (28–100) |
V | Suspicious for malignancy | 81% (40–100) |
VI | Malignant | 98% (86–100) |
Tier | Molecular Alteration | Risk of Invasive Disease | Surgical Approach | |
---|---|---|---|---|
1 | Point mutations
| Low | Lobectomy without central neck dissection provided no evidence of LN metastasis on US | Completion thyroidectomy if >2 vessel vascular invasion or high-grade histologic features |
2 | Point mutations
| Intermediate | Total thyroidectomy with prophylactic/therapeutic central neck dissection. Consider lobectomy with prophylactic central neck dissection if no evidence of LN metastasis on US. | Completion thyroidectomy if multifocality or ≥5 positive LNs |
3 | Fusions
| High |
Agent | Molecular Target(s) | Histology | n | Age (Years) | Response | Citation |
---|---|---|---|---|---|---|
Selpercatinib | RET | MTC | 14 | 2–20 2–20 | ORR 83.3% | [92] |
PTC | 10 | ORR 100% | ||||
2-year PFS 92.4% | ||||||
Larotrectinib | NTRK | Agnostic | 78 | 0.1–17.8 | ORR 88% | [100] |
94 | 0–18 | ORR 84% | [101] | |||
PTC | 2 | 6–13 | PR 50%, CR 50% | [95] | ||
Cabozantinib | VEGFR2, RET, MET, FLT3, NTRK, AXL | MTC | 5 | 1 | PR 40% | [102] |
Agent | Molecular Target(s) | Histology | Age (Years) | Location(s) | Status | ClinicalTrials.gov ID |
---|---|---|---|---|---|---|
Larotrectinib | NTRK | DTC | ≥1 | USA | Recruiting | NCT05783323 |
Repotrectinib | ALK, ROS1, NTRK | Agnostic | ≥12 | International | Recruiting | NCT03093116 |
Pralsetinib | RET | Agnostic | 0.5–21 | International | Active, not recruiting | NCT03899792 |
Pralsetinib | RET | Thyroid carcinoma | ≥12 | USA | Active, not recruiting | NCT04759911 |
Pralsetinib | RET | DTC | ≥12 | USA | Recruiting | NCT05668962 |
Pralsetinib | RET | Agnostic | ≥12 | International | Active, not recruiting | NCT03157128 |
Oncogene-specific kinase inhibitors | NTRK, RET, ALK, BRAFV600E | DTC | ≥0 | USA, Australia | Recruiting | NCT05024929 |
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Vanderniet, J.A.; Fuentes-Bolanos, N.A.; Cho, Y.H.; Tucker, K.M.; Anazodo, A.; Bauer, A.J.; Benitez-Aguirre, P.Z. Paediatric Thyroid Carcinoma: The Genetic Revolution and Its Implications for Therapy and Outcomes. Cancers 2025, 17, 1549. https://doi.org/10.3390/cancers17091549
Vanderniet JA, Fuentes-Bolanos NA, Cho YH, Tucker KM, Anazodo A, Bauer AJ, Benitez-Aguirre PZ. Paediatric Thyroid Carcinoma: The Genetic Revolution and Its Implications for Therapy and Outcomes. Cancers. 2025; 17(9):1549. https://doi.org/10.3390/cancers17091549
Chicago/Turabian StyleVanderniet, Joel A., Noemi A. Fuentes-Bolanos, Yoon Hi Cho, Katherine M. Tucker, Antoinette Anazodo, Andrew J. Bauer, and Paul Z. Benitez-Aguirre. 2025. "Paediatric Thyroid Carcinoma: The Genetic Revolution and Its Implications for Therapy and Outcomes" Cancers 17, no. 9: 1549. https://doi.org/10.3390/cancers17091549
APA StyleVanderniet, J. A., Fuentes-Bolanos, N. A., Cho, Y. H., Tucker, K. M., Anazodo, A., Bauer, A. J., & Benitez-Aguirre, P. Z. (2025). Paediatric Thyroid Carcinoma: The Genetic Revolution and Its Implications for Therapy and Outcomes. Cancers, 17(9), 1549. https://doi.org/10.3390/cancers17091549