<i>DICER1</i> Variants in Pediatric and Young Adult Thyroid Nodules

<b><i>Background:</i></b> Recent studies have suggested that pathogenic variants of the <i>DICER1</i> gene could be a driver of alterations in some pediatric thyroid nodules, but data are still limited. The aim of this study was to detect variants in the <i>DICER1</i> gene in a large cohort of pediatric thyroid nodules and then correlate them with clinicopathological data, with a focus on the disease prognosis in patients with thyroid carcinoma. <b><i>Methods:</i></b> This retrospective cohort study consisted of 350 pediatric and young adult patients (aged 2-21 years) with thyroid nodules, from whom 275 fresh-frozen thyroid nodule samples and 92 fine-needle aspiration biopsy (FNAB) samples were collected. After an analysis of variants in major genetic alterations of thyroid tumors, variants in the <i>DICER1</i> gene were identified using next-generation sequencing and multiplex ligation-dependent probe amplification methods. Peripheral blood was analyzed from patients with <i>DICER1</i>-positive tumors. The results of genetic analysis were then correlated with clinicopathological data. <b><i>Results:</i></b> Variants in the <i>DICER1</i> gene were detected in a total of 24/350 (6.9%; 95%CI [4.4;10.0]) pediatric and young adult patients, respectively, in 10/119 (8.4%; [4.1;14.9]) patients with benign fresh-frozen tissue, in 8/141 (5.7%; [1.9;9.5]) with papillary thyroid carcinoma (PTC) and in 6/86 (7.0%; [4.1;14.6]) patients with FNAB. No other gene alteration was found in <i>DICER1</i>-positive samples. Germline <i>DICER1</i> variants were identified in 11/24 (45.8%; [25.6;67.2]) patients. Two somatic (biallelic) variants in the <i>DICER1</i> gene were found in 9/24 (37.5%; [18.8;59.4]) thyroid nodules. Somatic deletions of at least 3 Mbp long were revealed in 2/24 (8.3%; [1.0;27.0]) cases. <i>DICER1</i>-positive PTCs were significantly associated with the follicular subtype of PTC (<i>p</i> = 0.001), encapsulation (<i>p</i> = 0.006) and were larger in size (<i>p</i> = 0.035), but with no extrathyroidal extension (<i>p</i> = 0.039), and less frequent lymph node metastases (<i>p</i> = 0.003) compared with <i>DICER1</i>-negative PTCs. Patients with <i>DICER1-</i>positive PTC had an excellent response to treatment in 75% of cases. <b><i>Conclusions:</i></b> Variants of the <i>DICER1</i> gene are frequently found in the thyroid nodules of pediatric and young adult patients. In our patients, <i>DICER1</i>-positive PTCs showed low invasiveness. Our findings support considering more conservative management for <i>DICER1</i>-positive low-risk PTCs.