Genomic landscape of sporadic pediatric differentiated thyroid cancers: a systematic review and meta-analysis

J Pediatr Endocrinol Metab. 2022 Apr 18;35(6):749-760. doi: 10.1515/jpem-2021-0741. Print 2022 Jun 27.


Objectives: Differentiated thyroid cancers (DTCs) in the paediatric population differ from that of their adult counterparts in terms of clinicopathological characteristics and treatment outcomes. This systematic review and meta-analysis was conducted to comprehensively evaluate the prevalence of various genetic alterations underlying the pathogenesis of sporadic paediatric DTCs.

Methods: This study followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Systematic searches were made on the PubMed and Embase databases using relevant keywords, and articles published until October 15, 2021 were selected. Data on the prevalence of various genetic alterations were extracted from the individual articles. Random-effects model was employed for meta-analysis to generate pooled estimates and their 95% confidence intervals (95% CIs).

Results: Thirty-three articles comprising 1,380 paediatric patients were included. RET rearrangement (pooled prevalence: 24.4%, 95% CI: 19.1-30.1) was observed to be the most common genetic alteration in sporadic paediatric DTCs, closely followed by BRAF point mutation (pooled prevalence: 21.2%, 95% CI: 17.2-25.5). Other common alterations included: NTRK rearrangement (pooled prevalence: 13.5%, 95% CI: 9.5-17.9) and DICER1 mutation (pooled prevalence: 12.5%, 95% CI: 3.6-25.7). RAS and TERT mutations were observed to be relatively uncommon (pooled prevalence: 5.7%, 95% CI: 2.9-9.3, and 2.2%, 95% CI: 0.4-5.5, respectively). There was no evidence of publication bias.

Conclusions: Fusion oncogenes are noted to be the major oncogenic drivers in sporadic paediatric DTCs and underlie their unique behaviour. However, despite the relatively lower frequency of BRAF point mutation compared to adults, it remains a major player in childhood DTCs.

Keywords: fusion oncogene; meta-analysis; mutation; paediatric thyroid cancer; rearrangement; systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Child
  • DEAD-box RNA Helicases / genetics
  • Genomics
  • Humans
  • Mutation
  • Point Mutation
  • Proto-Oncogene Proteins B-raf* / genetics
  • Ribonuclease III / genetics
  • Thyroid Neoplasms* / epidemiology
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / pathology


  • Proto-Oncogene Proteins B-raf
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases