Germline SUCLG2 Variants in Patients With Pheochromocytoma and Paraganglioma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00553062" target="_blank" >RIV/68378050:_____/22:00553062 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/86652036:_____/22:00553062 RIV/00098892:_____/22:10157578 RIV/60076658:12310/22:43905652 RIV/00216208:11310/22:10456127 RIV/61989592:15110/22:73610127

Výsledek na webu

<a href="https://academic.oup.com/jnci/article-abstract/114/1/130/6355591?redirectedFrom=fulltext&login=false" target="_blank" >https://academic.oup.com/jnci/article-abstract/114/1/130/6355591?redirectedFrom=fulltext&login=false</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/jnci/djab158" target="_blank" >10.1093/jnci/djab158</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Germline SUCLG2 Variants in Patients With Pheochromocytoma and Paraganglioma

Popis výsledku v původním jazyce

Background: Pheochromocytoma and paraganglioma (PPGL) are neuroendocrine tumors with frequent mutations in genes linked to the tricarboxylic acid cycle. However, no pathogenic variant has been found to date in succinyl-CoA ligase (SUCL), an enzyme that provides substrate for succinate dehydrogenase (SDH, mitochondrial complex II [CH]), a known tumor suppressor in PPGL. Methods: A cohort of 352 patients with apparently sporadic PPGL underwent genetic testing using a panel of 54 genes developed at the National Institutes of Health, including the SUCLG2 subunit of SUCL. Gene deletion, succinate levels, and protein levels were assessed in tumors where possible. To confirm the possible mechanism, we used a progenitor cell line, hPheo1, derived from a human pheochromocytoma, and ablated and re-expressed SUCLG2. Results: We describe 8 germline variants in the guanosine triphosphate-binding domain of SUCLG2 in 15 patients (15 of 352, 4.3%) with apparently sporadic PPGL. Analysis of SUCLG2-mutated tumors and SUCLG2-deficient hPheo1 cells revealed absence of SUCLG2 protein, decrease in the level of the SDHB subunit of SDH, and faulty assembly of the complex II, resulting in aberrant respiration and elevated succinate accumulation. Conclusions: Our study suggests SUCLG2 as a novel candidate gene in the genetic landscape of PPGL. Large-scale sequencing may uncover additional cases harboring SUCLG2 variants and provide more detailed information about their prevalence and penetrance.

Název v anglickém jazyce

Germline SUCLG2 Variants in Patients With Pheochromocytoma and Paraganglioma

Popis výsledku anglicky

Background: Pheochromocytoma and paraganglioma (PPGL) are neuroendocrine tumors with frequent mutations in genes linked to the tricarboxylic acid cycle. However, no pathogenic variant has been found to date in succinyl-CoA ligase (SUCL), an enzyme that provides substrate for succinate dehydrogenase (SDH, mitochondrial complex II [CH]), a known tumor suppressor in PPGL. Methods: A cohort of 352 patients with apparently sporadic PPGL underwent genetic testing using a panel of 54 genes developed at the National Institutes of Health, including the SUCLG2 subunit of SUCL. Gene deletion, succinate levels, and protein levels were assessed in tumors where possible. To confirm the possible mechanism, we used a progenitor cell line, hPheo1, derived from a human pheochromocytoma, and ablated and re-expressed SUCLG2. Results: We describe 8 germline variants in the guanosine triphosphate-binding domain of SUCLG2 in 15 patients (15 of 352, 4.3%) with apparently sporadic PPGL. Analysis of SUCLG2-mutated tumors and SUCLG2-deficient hPheo1 cells revealed absence of SUCLG2 protein, decrease in the level of the SDHB subunit of SDH, and faulty assembly of the complex II, resulting in aberrant respiration and elevated succinate accumulation. Conclusions: Our study suggests SUCLG2 as a novel candidate gene in the genetic landscape of PPGL. Large-scale sequencing may uncover additional cases harboring SUCLG2 variants and provide more detailed information about their prevalence and penetrance.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

JNCI-Journal of the National Cancer Institute

ISSN

0027-8874

e-ISSN

1460-2105

Svazek periodika

114

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

djab158

Kód UT WoS článku

000748167200019

EID výsledku v databázi Scopus

2-s2.0-85118371724