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Je něco špatně v tomto záznamu ?
Germline SUCLG2 Variants in Patients With Pheochromocytoma and Paraganglioma
K. Hadrava Vanova, Y. Pang, L. Krobova, M. Kraus, Z. Nahacka, S. Boukalova, SD. Pack, R. Zobalova, J. Zhu, TT. Huynh, I. Jochmanova, O. Uher, S. Hubackova, S. Dvorakova, TJ. Garrett, HK. Ghayee, X. Wu, B. Schuster, PE. Knapp, Z. Frysak, I....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Intramural, práce podpořená grantem
NLK
Free Medical Journals
od 1996 do Před 1 rokem
Open Access Digital Library
od 1996-01-01
PubMed
34415331
DOI
10.1093/jnci/djab158
Knihovny.cz E-zdroje
- MeSH
- feochromocytom * genetika patologie MeSH
- lidé MeSH
- nádory nadledvin * genetika patologie MeSH
- paragangliom * genetika patologie MeSH
- sukcinátdehydrogenasa genetika metabolismus MeSH
- zárodečné mutace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Intramural MeSH
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 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.
Department of Cell Biology Faculty of Science Charles University Prague Czech Republic
Institute of Biotechnology Czech Academy of Sciences BIOCEV Vestec Prague West Czech Republic
Institute of Molecular Genetics Czech Academy of Sciences Prague Czech Republic
School of Pharmacy and Medical Science Griffith University Southport QLD Australia
Section of Endocrinology Boston Medical Center Boston University Boston MA USA
Citace poskytuje Crossref.org
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