Complexity-increasing algorithm for the detection of molecular alterations in Differentiated Pediatric Thyroid Carcinoma

BOYCHO MARISA; COLLI SANDRA; MANGONE FRANCO; PAPENDIECK P.; MEDÍN M.; CHIESA A.; GRACIA LOMBARDI M.; DE MATTEO ELENA; PRECIADO VICTORIA; LORENZETTI MARIO

Mar del Plata

Congreso; Reunión de Sociedades de Biociencias SAIC-SAB-AAFE-AACyTAL; 2023

Differentiated thyroid carcinoma (DTC) is the most common tumor of the endocrine system in children and its incidence is rising. Molecular markers, either chromosome fusions or single nucleotide polymorphisms (SNPs) serve as prognostic and/or specific treatment-selection tools. Our aim was to characterize molecular alterations in a series of pediatric cases with DTC from Argentina and test a future laboratory algorithm for molecular diagnosis and stratification. FISH, IHC and Sanger sequencing were performed on 57 pediatric DTC biopsies enrolled between 2018 and 2022 at our hospital.The classic variant was predominant 25/57 (47%), followed by the Follicular variant 14/57 (25%). Initially, 4/57 (7%) cases were positive for pan-TRK by IHC and subsequently positive for NTRK3 by FISH. In independent FISH reactions, 2 cases were positive for ETV6 as the fusion partner. The 2 uncertain cases were solved by NGS and also found to be NTRK3-ETV6 fused. All negative cases were assessed for other fused genes by FISH. Considering all studied gene fusions, 17/57 (30%) harbored fusions in known oncogenes: 6 in RET (35%), 5 in ALK (29%), 4 NTRK3 (24%), 1 BRAF (6%) and 1 MET (6%). BRAF c.1799A>T (p.V600E) SNP was detected in 7/57 (12%) cases by Sanger sequencing. When relating clinico-pathological features with molecular markers, tumor size (T1/T2 vs T3/T4) was significantly larger in those DTC with genetic alterations (P=0.027) and, initial risk assessment (high/intermediate vs low risk) was also statistically higher for cases with genetic alterations (P=0.018).The most commonly fused gene was RET, followed by ALK and NTRK3. Gene fusions were more prevalent than V600E SNP. Designing a laboratory algorithm, following an increasing order of complexity, will provide a reliable molecular testing platform to reduce the requirement on NGS service, which is not available in all laboratories. These results also broaden data on DTC alterations in children from our own geographic region.