{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:27:18Z","timestamp":1792794438863,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Intramural Research Program of the National Institutes of Health"},{"name":"National Institute of Child Health and Human Development and National Cancer Institute"},{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["18-10832S"],"award-info":[{"award-number":["18-10832S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["19-20553S"],"award-info":[{"award-number":["19-20553S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["20-11724Y"],"award-info":[{"award-number":["20-11724Y"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["20-05942S"],"award-info":[{"award-number":["20-05942S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Czech Health Foundation","award":["17-30138A"],"award-info":[{"award-number":["17-30138A"]}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Program of Ministry of Education Youth and Sports of the Czech Republic","award":["LM2018130"],"award-info":[{"award-number":["LM2018130"]}],"id":[{"id":"https:\/\/ror.org\/037n8p820","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We describe 8 germline variants in the guanosine triphosphate\u2013binding 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djab158","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T15:15:25Z","timestamp":1629299725000},"page":"130-138","source":"Crossref","is-referenced-by-count":33,"title":["Germline\n                    <i>SUCLG2<\/i>\n                    Variants in Patients With Pheochromocytoma and Paraganglioma"],"prefix":"10.1093","volume":"114","author":[{"given":"Katerina","family":"Hadrava Vanova","sequence":"first","affiliation":[{"name":"Section of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA"},{"name":"Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Prague West, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Pang","sequence":"additional","affiliation":[{"name":"Section of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Krobova","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Prague West, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Kraus","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Prague West, Czech Republic"},{"name":"Department of Cell Biology, Faculty of Science, Charles University, Prague, Czech 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