THU679 Genetic Alterations In Children And Young Adults Differentiated Thyroid Cancer
Authors: Rodríguez Machado Gabriel Jeferson , Oliveira Tosta Telles Ana Clara , von Ammon Juliana Lima , Campos da Matta Rafael Reis , de Lima Beltrão Fabyan Esberard , Hecht Fábio , da Paz Alexandre Rolim , Castro Lopes Guilherme de , Boaventura Rios Leonardo Freitas , Ramos Helton Estrela 
Published: October 2023

Disclosure: G.J. Machado: None. A.O. Telles: None. J.L. von Ammon: None. R.R. da Matta: None. F.E. Beltrão: None. F. Hecht: None. A.R. da Paz: None. G.D. Lopes: None. L.F. Rios: None. H.E. Ramos: None.

Introduction: Children and young adults (CAYA) differentiated thyroid cancer (DTC) differs from adult DTC in its underlying genetics features. In this report, we studied these aspects in 79 cases of CAYA DTC. Objective: To determine the prevalence of molecular alterations in paraffin-embedded samples of DTC from children, adolescents and young adults treated at the centers participating in the study. Methods: Tumor samples obtained from 79 CAYA patients (age &lt; 21 years) screened with DTC between January 2010 and Mach 2021 were retrospectively recruited from four health centers from the state of Bahia and Paraíba, Brazil. Demographic and anatomopathological data were reviewed by a pathologist. Tumor DNA was extracted from paraffin-embedded samples and directed to analysis through next-generation sequencing (NGS), where it was submitted to the HotSpot panel to determine point mutations, and to the Fusion Panel to identify gene fusions. Results: The median age at diagnosis observed in the sample studied was 18 years, with patients ranging between 6 and 21 years. Thirty patients (38%) were under 18 years and forty-nine (62%) were aged between 18 and 21 years. The vast majority were female (77%), with only 18 cases male (23%). Overall: 21/79 (26.6%) results were inconclusive, 21/79 (26.6%) mutated and 37/79 (46.8%) wild type. Among the mutated, 10/21 (47.6%) cases were positive for BRAF mutation, 08/21 (38.1%) for EGFR, 04/21 (19.0%) for KRAS, 03/21 (14 .3%) for NRAS and 01/21 (4.8%) for PIK3CA, with occurrence of simultaneous point mutations. Of the 10 mutations found in the BRAF gene, 60% of them were V600E. The remaining percentage was characterized by less common genetic alterations in this gene, the so-called BRAFnon-V600E, were identified: 01 BRAFG464R mutation, 01 BRAFG469E and 02 BRAFS467L. As for molecular analysis to detect gene fusions: 39/74 (52.7%) had inconclusive results, 10/74 (13.5%) were positive for a rearrangement and 25/74 (33.8%) were classified as wild type. Among the positive cases for gene fusions: 03 were of the RET gene (01 CCDC6::RET or RET/PTC1, 01 NCOA4::RET or RET/PTC3, and 01 TRIM24::RET or RET/PTC6); 04 were from the NTRK gene (03 ETV6::NTRK3 and 01 TPR::NTRK1); 02 PAX8::PPARG merges; and 01 STRN::ALK. Conclusion: In our CAYA patients: (i) BRAF gene mutations were the most prevalent, followed by EGFR, KRAS, NRAS and PIK3CA, (ii) novel BRAFnon-V600E were identified, (iii) 13,5% had gene rearrangements which were more frequent in subjects under 18 years old. *Supported by Bayer (21641)

Presentation: Thursday, June 15, 2023