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DICER1 Variants in Pediatric and Young Adult Thyroid Nodules.

Authors :
Mastnikova, Karolina
Bulanova Pekova, Barbora
Kuklikova, Vlasta
Vaclavikova, Eliska
Carkova, Jitka
Katra, Rami
Fialova, Lucie
Vlcek, Petr
Kodetova, Daniela
Chovanec, Martin
Drozenova, Jana
Matej, Radoslav
Pacesova, Petra
Novak, Zdenek
Procykova, Kristyna
Vcelak, Josef
Bendlova, Bela
Source :
Thyroid. Oct2024, Vol. 34 Issue 10, p1225-1233. 9p.
Publication Year :
2024

Abstract

Background: Recent studies have suggested that pathogenic variants of the DICER1 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 DICER1 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. Methods: 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 DICER1 gene were identified using next-generation sequencing and multiplex ligation-dependent probe amplification methods. Peripheral blood was analyzed from patients with DICER1-positive tumors. The results of genetic analysis were then correlated with clinicopathological data. Results: Variants in the DICER1 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 DICER1-positive samples. Germline DICER1 variants were identified in 11/24 (45.8%; [25.6;67.2]) patients. Two somatic (biallelic) variants in the DICER1 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. DICER1-positive PTCs were significantly associated with the follicular subtype of PTC (p = 0.001), encapsulation (p = 0.006) and were larger in size (p = 0.035), but with no extrathyroidal extension (p = 0.039), and less frequent lymph node metastases (p = 0.003) compared with DICER1-negative PTCs. Patients with DICER1-positive PTC had an excellent response to treatment in 75% of cases. Conclusions: Variants of the DICER1 gene are frequently found in the thyroid nodules of pediatric and young adult patients. In our patients, DICER1-positive PTCs showed low invasiveness. Our findings support considering more conservative management for DICER1-positive low-risk PTCs. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10507256
Volume :
34
Issue :
10
Database :
Academic Search Index
Journal :
Thyroid
Publication Type :
Academic Journal
Accession number :
180233657
Full Text :
https://doi.org/10.1089/thy.2024.0188