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Genetic alterations landscape in paediatric thyroid tumours and/or differentiated thyroid cancer: Systematic review

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Abstract

Differentiated thyroid cancer (DTC) is a rare disease in the paediatric population (≤ 18 years old. at diagnosis). Increasing incidence is reflected by increases in incidence for papillary thyroid carcinoma (PTC) subtypes. Compared to those of adults, despite aggressive presentation, paediatric DTC has an excellent prognosis. As for adult DTC, European and American guidelines recommend individualised management, based on the differences in clinical presentation and genetic findings. Therefore, we conducted a systematic review to identify the epidemiological landscape of all genetic alterations so far investigated in paediatric populations at diagnosis affected by thyroid tumours and/or DTC that have improved and/or informed preventive and/or curative diagnostic and prognostic clinical conduct globally. Fusions involving the gene RET followed by NTRK, ALK and BRAF, were the most prevalent rearrangements found in paediatric PTC. BRAF V600E was found at lower prevalence in paediatric (especially ≤ 10 years old) than in adults PTC. We identified TERT and RAS mutations at very low prevalence in most countries. DICER1 SNVs, while found at higher prevalence in few countries, they were found in both benign and DTC. Although the precise role of DICER1 is not fully understood, it has been hypothesised that additional genetic alterations, similar to that observed for RAS gene, might be required for the malignant transformation of these nodules. Regarding aggressiveness, fusion oncogenes may have a higher growth impact compared with BRAF V600E. We reported the shortcomings of the systematized research and outlined three key recommendations for global authors to improve and inform precision health approaches, glocally.

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Acknowledgements

This work was supported by research grant 406952/2022-1 from the Ministry of Health, Brazil, and research grants 2014/06570-6 and 2022/09713-9 from the São Paulo State Research Foundation (FAPESP). INN and YPC are CAPES scholars. MSAS is a Brazilian Research Council (CNPq) scholar. JMC is a CNPq investigator. The authors thank Mabel F Figueiró for supporting protocol development and validation, and systematic review methodology revision.

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  1. Genetic Bases of Thyroid Tumours Laboratory, Division of Genetics, Department of Morphology and Genetics and Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, 11 andar, São Paulo, SP, 04039-032, Brazil

    Maria Sharmila Alina de Sousa, Isabela Nogueira Nunes, Yasmin Paz Christiano, Luiza Sisdelli & Janete Maria Cerutti

  2. PreScouter Inc., 29 E Madison St #500, Chicago, IL, 60602, USA

    Luiza Sisdelli

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MSAS and JMC made substantial contributions to the conception or design of the work; MSAS, INN, YPC, LS and JMC made substantial contributions to the acquisition, analysis, or interpretation of data; MSAS, INN, YPC, LS and JMC drafted the work or revised it critically for important intellectual content; all authors approved the version to be published; and MSAS, INN, YPC, LS and JMC agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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de Sousa, M.S.A., Nunes, I.N., Christiano, Y.P. et al. Genetic alterations landscape in paediatric thyroid tumours and/or differentiated thyroid cancer: Systematic review. Rev Endocr Metab Disord 25, 35–51 (2024). https://doi.org/10.1007/s11154-023-09840-2

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