DICER1 Variants in Pediatric and Young Adult Thyroid Nodules

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023761%3A_____%2F24%3AN0000032" target="_blank" >RIV/00023761:_____/24:N0000032 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/24:43927556 RIV/00216208:11130/24:10485494 RIV/00064173:_____/24:43927556 RIV/00064203:_____/24:10485494

Výsledek na webu

<a href="https://doi.org/10.1089/thy.2024.0188" target="_blank" >https://doi.org/10.1089/thy.2024.0188</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1089/thy.2024.0188" target="_blank" >10.1089/thy.2024.0188</a>

Jazyk výsledku

angličtina

Název v původním jazyce

DICER1 Variants in Pediatric and Young Adult Thyroid Nodules

Popis výsledku v původním jazyce

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 to 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.

Název v anglickém jazyce

DICER1 Variants in Pediatric and Young Adult Thyroid Nodules

Popis výsledku anglicky

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 to 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/NU21-01-00448" target="_blank" >NU21-01-00448: Nové diagnostické a prognostické markery v preoperační a postoperační péči o pacienty s nádory štítné žlázy</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Thyroid

ISSN

1050-7256

e-ISSN

1557-9077

Svazek periodika

34

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

1225-1233

Kód UT WoS článku

001321088600001

EID výsledku v databázi Scopus

2-s2.0-85205724818