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Evaluation of the genetic alterations landscape of differentiated thyroid cancer in children

  • Ebru Barsal Çetiner ORCID logo , Mualla Özcan ORCID logo , Mustafa Aydemir ORCID logo , Zeynep Donbaloğlu ORCID logo , Berna Singin ORCID logo , Bilge Aydın Behram ORCID logo , Aynur Bedel ORCID logo , Güzide Ayşe Ocak ORCID logo , İnanç Elif Gürer ORCID logo , Güngör Karagüzel ORCID logo , Mesut Parlak ORCID logo and Hale Tuhan ORCID logo EMAIL logo
Published/Copyright: November 3, 2025
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 12

Abstract

Objectives

Studies investigating the underlying genetic profile in pediatric patients diagnosed with differentiated thyroid cancer (DTC) are quite limited. This study aimed to identify genetic alterations in patients diagnosed with DTC.

Methods

A total of 20 patients with confirmed DTC were included in the study; however, five were excluded due to the unavailability of thyroid tumor samples. Somatic mutation analysis of the DICER1, BRAF, KRAS, NRAS, and HRAS genes was performed using next-generation sequencing. In addition, gene fusions involving ALK, RET, PTC, ETV6, and NTRK3 were assessed using fluorescence in situ hybridization. A family screening was also conducted, and thyroid ultrasonography was performed. Fine-needle aspiration biopsy was carried out for family members when deemed necessary.

Results

The mean age at diagnosis was 14.42 ± 2.88 years. Somatic mutations were identified in nine patients (60 %). The detected mutations were as follows: RET/PTC fusion (n=3), BRAF V600E (n=2), NRAS Q61R (n=1), NRAS A59D (n=1), DICER1 E1705K (n=1), and ETV6/NTRK3 fusion (n=1). No statistically significant differences in prognostic factors were observed between patients with and without somatic mutations. As part of the family screening, suspicious thyroid nodules were detected in four parents. One parent underwent hemithyroidectomy, and final pathology revealed papillary thyroid carcinoma.

Conclusions

Considering the limited number of similar studies on childhood thyroid cancer, these findings provide a valuable contribution to the existing literature. In particular, the results obtained from family screening may support advancements in early diagnosis, risk stratification, and the development of targeted therapeutic approaches.

Keywords: pediatric differentiated thyroid cancer; NGS; fusion-oncogenes; BRAF; RET-PTC
Corresponding author: Hale Tuhan, MD, Department of Pediatric Endocrinology, Akdeniz University Faculty of Medicine Hospital, Konyaalti, 07070, Antalya, Türkiye, E-mail:

  1. Research ethics: The study was conducted in accordance with the principles of the Declaration of Helsinki. The study was authorized by the Ethics Committee of our University (Approval date: 03/16/2022, Approval No: KAEK-133). Informed consent was obtained from all participants or their legal guardians before inclusion in the study.

  2. Informed consent: Informed consent was obtained from all participants or their legal guardians before inclusion in the study.

  3. Author contributions: Conceptualization: H. T., E. B.Ç.; Data curation: E. B. Ç., M. Ö., Z. D., B. S., B. A. B., A. B.; Formal analysis and investigation: M. Ö., G. A. O., İ. E. G., E. B. Ç., M. A., G. K.; Methodology: H. T., M. Ö., G. A. O., İ. E. G.; Funding acquisition: H. T.; Resources: H. T., M. P.; Supervision: H. T., M. P.; Writing – original draft preparation: E. B. Ç., M. Ö.; Writing – review and editing: E. B. Ç., H. T., M. P.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: This research was funded by the Scientific Research Projects Coordination Unit of Akdeniz University (Project number: TSA-2023-6115).

  7. Data availability: No datasets were generated or analysed during the current study.

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Received: 2025-06-24
Accepted: 2025-10-10
Published Online: 2025-11-03
Published in Print: 2025-12-17

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Subclinical but significant? Updated review of pediatric hypothyroidism
  4. Original Articles
  5. The differential impact of automated insulin delivery systems on body mass index in children with type 1 diabetes
  6. Maturity-onset diabetes of the young due to HNF1β variants (HNF1β-MODY): a 2-year follow-up study of six patients from a single diabetes center
  7. Investigating the kynurenine pathway in pediatric metabolic health
  8. Mucolipidosis type II and III: clinical spectrum, genetic landscape, and longitudinal outcomes in a pediatric cohort with six novel mutations
  9. Evaluation of the genetic alterations landscape of differentiated thyroid cancer in children
  10. Prognostic analysis of persistent disease in medium-to high-risk children and adolescents with differentiated thyroid carcinoma
  11. The clinical picture of symptomatic Rathke cleft cysts in children
  12. Pitfalls in the diagnosis of carnitine palmitoyltransferase 1 deficiency
  13. Effective treatment of hyperphosphatemia with denosumab in patients with loss of function of FGF23 and high bone density: case series
  14. Case Reports
  15. Dual molecular genetic diagnosis with combined malonic and methylmalonic aciduria (CMAMMA): implications of coexisting genetic disorders on clinical presentation
  16. Family experience with individuals of different ages and clinical presentations diagnosed with DI: do familial DI cases tolerate polyuria better?
  17. Atypical pediatric presentation of hyperparathyroidism: CDC73 gene mutation and parathyroid carcinoma
  18. Pseudohypertriglyceridemia as a clue: clinical and genetic spectrum of glycerol kinase deficiency in three pediatric cases
  19. Transient worsening of thyrotoxic myopathy following methimazole and metoprolol initiation in a 12-year-old girl: a case report and literature review
  20. Letter to the Editor
  21. Cognitive behavioral therapy (CBT) effect on diabetic youth depression, death anxiety and glycemic control
  22. Annual Reviewer Acknowledgment
  23. Reviewer Acknowledgment
https://doi.org/10.1515/jpem-2025-0443
Keywords for this article
pediatric differentiated thyroid cancer; NGS; fusion-oncogenes; BRAF; RET-PTC

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Subclinical but significant? Updated review of pediatric hypothyroidism
  4. Original Articles
  5. The differential impact of automated insulin delivery systems on body mass index in children with type 1 diabetes
  6. Maturity-onset diabetes of the young due to HNF1β variants (HNF1β-MODY): a 2-year follow-up study of six patients from a single diabetes center
  7. Investigating the kynurenine pathway in pediatric metabolic health
  8. Mucolipidosis type II and III: clinical spectrum, genetic landscape, and longitudinal outcomes in a pediatric cohort with six novel mutations
  9. Evaluation of the genetic alterations landscape of differentiated thyroid cancer in children
  10. Prognostic analysis of persistent disease in medium-to high-risk children and adolescents with differentiated thyroid carcinoma
  11. The clinical picture of symptomatic Rathke cleft cysts in children
  12. Pitfalls in the diagnosis of carnitine palmitoyltransferase 1 deficiency
  13. Effective treatment of hyperphosphatemia with denosumab in patients with loss of function of FGF23 and high bone density: case series
  14. Case Reports
  15. Dual molecular genetic diagnosis with combined malonic and methylmalonic aciduria (CMAMMA): implications of coexisting genetic disorders on clinical presentation
  16. Family experience with individuals of different ages and clinical presentations diagnosed with DI: do familial DI cases tolerate polyuria better?
  17. Atypical pediatric presentation of hyperparathyroidism: CDC73 gene mutation and parathyroid carcinoma
  18. Pseudohypertriglyceridemia as a clue: clinical and genetic spectrum of glycerol kinase deficiency in three pediatric cases
  19. Transient worsening of thyrotoxic myopathy following methimazole and metoprolol initiation in a 12-year-old girl: a case report and literature review
  20. Letter to the Editor
  21. Cognitive behavioral therapy (CBT) effect on diabetic youth depression, death anxiety and glycemic control
  22. Annual Reviewer Acknowledgment
  23. Reviewer Acknowledgment
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