Germline SUCLG2 Variants in Patients With Pheochromocytoma and Paraganglioma
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F22%3A73610127" target="_blank" >RIV/61989592:15110/22:73610127 - isvavai.cz</a>
Result on the web
<a href="https://academic.oup.com/jnci/article-abstract/114/1/130/6355591?redirectedFrom=fulltext" target="_blank" >https://academic.oup.com/jnci/article-abstract/114/1/130/6355591?redirectedFrom=fulltext</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/jnci/djab158" target="_blank" >10.1093/jnci/djab158</a>
Alternative languages
Result language
angličtina
Original language name
Germline SUCLG2 Variants in Patients With Pheochromocytoma and Paraganglioma
Original language description
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; CII), a known tumor suppressor in PPGL. Methods A cohort of 352 subjects 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 eight germline variants in the GTP-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 CII and faulty assembly of the complex, 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.
Czech name
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Czech description
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Classification
Type
J<sub>SC</sub> - Article in a specialist periodical, which is included in the SCOPUS database
CEP classification
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OECD FORD branch
30202 - Endocrinology and metabolism (including diabetes, hormones)
Result continuities
Project
<a href="/en/project/LM2018130" target="_blank" >LM2018130: National Infrastructure for Chemical Biology</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of the National Cancer Institute. Monographs
ISSN
1052-6773
e-ISSN
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Volume of the periodical
114
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
130-138
UT code for WoS article
000748167200019
EID of the result in the Scopus database
2-s2.0-85118371724