RET, NTRK, ALK, BRAF, and MET Fusions in a Large Cohort of Pediatric Papillary Thyroid Carcinomas

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F20%3A43920301" target="_blank" >RIV/00216208:11120/20:43920301 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61383082:_____/20:00000959 RIV/00216208:11130/20:10412633 RIV/00023761:_____/20:N0000016 RIV/00064203:_____/20:10412633

Výsledek na webu

<a href="https://doi.org/10.1089/thy.2019.0802" target="_blank" >https://doi.org/10.1089/thy.2019.0802</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1089/thy.2019.0802" target="_blank" >10.1089/thy.2019.0802</a>

Jazyk výsledku

angličtina

Název v původním jazyce

RET, NTRK, ALK, BRAF, and MET Fusions in a Large Cohort of Pediatric Papillary Thyroid Carcinomas

Popis výsledku v původním jazyce

Background:Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy, but with increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients. Methods:The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples, followed by DNA and RNA-targeted next-generation sequencing analyses. Fusion gene-positive samples were verified by real-time polymerase chain reaction. Results:A genetic alteration was found in 72/93 (77.4%) pediatric PTC cases. In 52/93 (55.9%) pediatric PTC patients, a fusion gene was detected. Twenty different types ofRET,NTRK3,ALK,NTRK1,BRAF, andMETfusions were found, of which five novel,TPR/RET,IKBKG/RET,BBIP1/RET,OPTN/BRAF, andEML4/MET, rearrangements were identified and aCUL1/BRAFrearrangement that has not been previously described in thyroid cancer. Fusion gene-positive PTCs were significantly associated with the mixture of classical and follicular variants of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis, and frequent occurrence of psammoma bodies compared with fusion gene-negative PTCs. Fusion-positive patients also received more doses of radioiodine therapy. The most common fusion genes were theRETfusions, followed byNTRK3fusions.RETfusions were associated with more frequent lymph node and distant metastases and psammoma bodies, andNTRK3fusions were associated with the follicular variant of PTC. Conclusions:Fusion genes were the most common genetic alterations in pediatric PTCs. Fusion gene-positive PTCs were associated with more aggressive disease than fusion gene-negative PTCs.

Název v anglickém jazyce

RET, NTRK, ALK, BRAF, and MET Fusions in a Large Cohort of Pediatric Papillary Thyroid Carcinomas

Popis výsledku anglicky

Background:Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy, but with increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients. Methods:The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples, followed by DNA and RNA-targeted next-generation sequencing analyses. Fusion gene-positive samples were verified by real-time polymerase chain reaction. Results:A genetic alteration was found in 72/93 (77.4%) pediatric PTC cases. In 52/93 (55.9%) pediatric PTC patients, a fusion gene was detected. Twenty different types ofRET,NTRK3,ALK,NTRK1,BRAF, andMETfusions were found, of which five novel,TPR/RET,IKBKG/RET,BBIP1/RET,OPTN/BRAF, andEML4/MET, rearrangements were identified and aCUL1/BRAFrearrangement that has not been previously described in thyroid cancer. Fusion gene-positive PTCs were significantly associated with the mixture of classical and follicular variants of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis, and frequent occurrence of psammoma bodies compared with fusion gene-negative PTCs. Fusion-positive patients also received more doses of radioiodine therapy. The most common fusion genes were theRETfusions, followed byNTRK3fusions.RETfusions were associated with more frequent lymph node and distant metastases and psammoma bodies, andNTRK3fusions were associated with the follicular variant of PTC. Conclusions:Fusion genes were the most common genetic alterations in pediatric PTCs. Fusion gene-positive PTCs were associated with more aggressive disease than fusion gene-negative PTCs.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

<a href="/cs/project/NV16-32665A" target="_blank" >NV16-32665A: Nádory štítné žlázy u dětí a dospívajících a jejich molekulárně genetická podstata</a><br>

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Thyroid

ISSN

1050-7256

e-ISSN

—

Svazek periodika

30

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

1771-1780

Kód UT WoS článku

000547647800001

EID výsledku v databázi Scopus

2-s2.0-85088828876