Endocrine Abstracts

Objectives: Mutations in the DICER1 gene represent driver events in development of pediatric thyroid nodules, malignant as well as benign. The occurrence of these mutations has been reported in differentiated thyroid carcinomas, poorly differentiated thyroid carcinomas, non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), multinodular goiters and follicular adenomas. The aim of this study was to detect mutations in DICER1 gene in a large cohort of pediatric thyroid nodules and correlate found mutations with clinicopathological data with a focus on prognosis of disease in patients with papillary thyroid carcinoma (PTC).

Methods: The study consisted of 132 thyroid nodule samples from 124 pediatric patients (age 6-20 years). The cohort included 110 PTCs, 2 NIFTPs and 20 benign nodules. DNA was isolated from fresh frozen thyroid tissues using the Allprep DNA/RNA/miRNA Universal kit and the QIAcube Connect Extraction System (Qiagen, Germany). DNA was used for next-generation sequencing on MiSeq sequencer (Illumina, USA) using the Nextera XT DNA Library Prep Kit (Illumina). Mutations in the DICER1 gene were visualized in Integrative Genomics Viewer (Broad Institute, USA) and evaluated by VarSome platform (Saphetor SA, Switzerland).

Results: Pathogenic DICER1 hotspot mutations (E1705K, D1709 N, E1813D) in 7 of 132 (5.3 %) pediatric thyroid samples were detected. Six of them were PTCs (follicular variant), from which 5 were encapsulated. Five PTC patients received only one dose (100 mCi) of radioiodine treatment and are in remission. Only in one case, the patient received three doses of radioiodine (2× 100 mCi, 1× 120 mCi). This patient had a 60-mm carcinoma and angioinvasion was described only in this patient. The DICER1 alteration was also found in one NIFTP case. All DICER1-mutated tumors did not possess other driver mutations (in the BRAF gene, RAS genes, fusion genes).

Conclusion: In summary, DICER1 mutations are important molecular markers in pediatric thyroid nodules. Almost all our DICER1-mutated carcinomas represented low-risk malignancies and patients had an excellent response to the treatment. However, one patient had an incomplete response to treatment due to the advanced stage at the time of diagnosis. In conclusion, DICER1-mutated tumors appear to be indolent, but should not be underestimated.

Supported by AZV NU21-01-00448 and MH CR RVO 00023761.