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

Author(s)

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

• Document type: Journal article
• Source: REVIEWS IN ENDOCRINE & METABOLIC DISORDERS; v. 25, n. 1, p. 17-pg., 2023-10-24.

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. (AU)

• FAPESP's process: 14/06570-6 - Comprehensive whole exome, paired-end RNA and genome sequencing: new insights into genetic bases of thyroid carcinoma in pediatric and adult ages and applications in clinical practice
• Grantee: Janete Maria Cerutti
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/09713-9 - Identification of predisposing genes to development of Familial Non-Medullary Thryoid Cancer using whole exoma sequencing
• Grantee: Janete Maria Cerutti
• Support Opportunities: Regular Research Grants