Počet záznamů: 1
Germline SUCLG2 Variants in Patients With Pheochromocytoma and Paraganglioma
- 1.
SYSNO ASEP 0553062 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Germline SUCLG2 Variants in Patients With Pheochromocytoma and Paraganglioma Tvůrce(i) Váňová Hadrava, Kateřina (BTO-N)
Pang, Y. (US)
Krobová, Linda (BTO-N)
Kraus, Michal (BTO-N)
Nahácka, Zuzana (BTO-N)
Boukalová, Štěpána (BTO-N)
Pack, S. (US)
Zobalová, Renata (BTO-N) RID
Zhu, J. (US)
Huynh, T.-T. (US)
Jochmanová, I. (SK)
Uher, O. (US)
Hubáčková, Soňa (BTO-N)
Dvořáková, Šárka (BTO-N) ORCID
Garrett, T. (US)
Ghayee, H. (US)
Wu, X. (US)
Schuster, Bjorn (UMG-J)
Knapp, P. (US)
Frysak, Z. (CZ)
Hartmann, I. (CZ)
Nilubol, N. (US)
Černý, Jiří (BTO-N) RID, ORCID
Taieb, D. (FR)
Rohlena, Jakub (BTO-N) RID, ORCID
Neužil, Jiří (BTO-N) RID
Yang, C. (US)
Pacak, K. (US)Celkový počet autorů 28 Číslo článku djab158 Zdroj.dok. JNCI-Journal of the National Cancer Institute . - : OXFORD UNIV PRESS INC - ISSN 0027-8874
Roč. 114, č. 1 (2022)Poč.str. 9 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova mutations ; deficiency ; penetrance ; phenotype ; genotype Vědní obor RIV FD - Onkologie a hematologie Obor OECD Oncology CEP GA18-10832S GA ČR - Grantová agentura ČR GA19-20553S GA ČR - Grantová agentura ČR GJ20-11724Y GA ČR - Grantová agentura ČR GA20-05942S GA ČR - Grantová agentura ČR LM2018130 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy NV17-30138A GA MZd - Ministerstvo zdravotnictví Způsob publikování Open access Institucionální podpora BTO-N - RVO:86652036 ; UMG-J - RVO:68378050 UT WOS 000748167200019 EID SCOPUS 85118371724 DOI 10.1093/jnci/djab158 Anotace 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. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2023 Elektronická adresa https://academic.oup.com/jnci/article-abstract/114/1/130/6355591?redirectedFrom=fulltext&login=false
Počet záznamů: 1