ESPE Abstracts

Background: Our study aimed to determine the molecular characterization of thyroid nodules and cancer in childhood and investigate the genotype-phenotype relationship.

Methods: The pre-postoperative clinical follow-up features and genetic characteristics of 62 patients were evaluated. Next-generation sequencing (NGS) was used to investigate common variants in thyroid lesions with sufficient tissue in the pathology archive. The patients were divided into three groups based on their pathological diagnoses: malignant, benign, and other(under follow-up). In patient samples classified as BC II-VI with sufficient tissue material in the pathology archive, DNA NGS was used to evaluate variants in 34genes(AKT1,ALK,ARID1B,APC,ATM,BRAF,CDKN2A,CDKNB1,DICER1,DNMT3A,EIF1AX,EZH1,FOXE1,GNAS,HABP2,HRAS,KRAS,LPAR4,MUTYH,NRAS,PIK3CA,POT1,PPM1D,PTEN,RET,SRRM2,TERT,NKX2-1,TP53,TSHR,ZFHX3,RBM10,MED12,PLEKHS1),and RNA NGS was used to evaluate variants in RET,ALK,CREB3L2,NTRK1,NTRK2,NTRK3,BRAF,EML4,PPARG,IGF2BP3.

Results: The mean age of 62 patients(50F/12M) was 14.2±3.5(min.:2.7; max.:19 years). Of these,37(59.7%) had differentiated thyroid cancers (DTC),2(3.2%) had low-risk tumors,14(22.6%) had benign, and 9(14.5%) had other cytological findings. The genes with detected pathological variants n 80%(n = 31) of DTC, listed in order of frequency, were as follows: BRAF (n = 13), P53 (n = 3), NCOA4-RET (n = 3), CCDC6-RET (n = 3), DICER (n = 2), NRAS (n = 2), TSHR (n = 1), ALK-STRN (n = 1), TPR-NTRK1 (n = 1), HRAS (n = 1), NTRK3-ETV6 (n = 1). BRAFV600E was the most common variant(%37). RET, NTRK, and ALK fusions were observed in 32%. In the benign group, four had pathogenic variants in DICER, TSHR, and PTEN. Among patients in BC, four patients in BC-II(n = 14), six patients in BC-III(n = 16), and seven patients in BC-IV (n = 10) had DTC. All in BC-V and VI were diagnosed with papillary thyroid cancer (PTC). Pathogenic variants in DICER (n = 1), p53 (n = 1), and PTEN (n = 1) were detected in patients diagnosed with DTC in BC-II. According to the ATA Guideline,28 patients were at low risk, eight were at moderate risk, and three were at high risk of DTC. Among high-risk patients, one had NCOA4-RET fusion; two had BRAFV600E. A 31-year-old patient initially diagnosed with BC-III and had a lobectomy 16 years ago was reevaluated due to the detection of BRAFV600E. He had no pathological findings in recent control. Among five patients with persistent disease and PTC diagnosis, four had BRAFV600E. A patient with distant metastasis at diagnosis had NCOA4-RET. BRAFV600E (n = 6), NCOA4-RET (n = 3), NTRK3-ETV6 (n = 1), and TPR-NTRK1 (n = 1) fusions were found in 16 PTC patients with lymph node involvement.

Conclusion: In this study, BRAFV600E and RET, NTRK, and ALK fusions were the most common pathogenic variants in children with DTC. BRAFV600E and NCOA4-RET fusion were seen in patients at high risk. Molecular studies contribute to patient management in cases initially diagnosed as BC-II-III with subsequent DTC diagnosis during follow-up.