{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T18:53:10Z","timestamp":1782327190633,"version":"3.54.5"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Oncometabolite production plays a key role in the development and progression of isocitrate dehydrogenase-mutant gliomas. The aberrant gain-of-function activity of the mutant isocitrate dehydrogenase protein results in the production of the oncometabolite D-2-hydroxyglutarate, which in turn promotes DNA hypermethylation and gliomagenesis through several mechanisms. Rare gliomas in patients with fumarate hydratase deficiency syndrome share many morphologic and molecular features with isocitrate dehydrogenase-mutant gliomas, with the oncometabolites succinate and 2-succinocysteine similarly thought to promote global DNA hypermethylation. Like isocitrate dehydrogenase and fumarate hydratase, succinate dehydrogenase is also a member of the citric acid cycle that additionally participates in oxidative phosphorylation. While succinate dehydrogenase deficiency has been implicated in familial tumor syndromes, it has not yet been associated with glial neoplasms. Here we report 3 cases of diffuse glioma with succinate dehydrogenase deficiency that show many similarities with isocitrate dehydrogenase-mutant gliomas. We propose that succinate dehydrogenase deficiency with accumulation of the oncometabolite succinate can promote gliomagenesis in a similar manner as seen in isocitrate dehydrogenase-mutant and fumarate hydratase-deficient gliomas, and we discuss the proposed mechanisms that may lead to tumor formation.<\/jats:p>","DOI":"10.1093\/jnen\/nlag004","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T12:28:42Z","timestamp":1768652922000},"page":"789-796","source":"Crossref","is-referenced-by-count":0,"title":["Gliomas with succinate dehydrogenase deficiency: A case series and brief review of the literature of oncometabolite-driven gliomagenesis"],"prefix":"10.1093","volume":"85","author":[{"given":"Madison T","family":"Gray","sequence":"first","affiliation":[{"name":"Pathology (Neuropathology), Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al , Montreal, QC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Cayrol","sequence":"additional","affiliation":[{"name":"Pathology (Neuropathology), Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al , Montreal, QC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"May","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Skaugen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Genomic Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Hayek","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Ascension St Vincent , Indianapolis, IN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lapointe","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al , Montreal, QC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia E","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Division of Pathology, The Hospital for Sick Children , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5712-9492","authenticated-orcid":false,"given":"Thomas M","family":"Pearce","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drew","family":"Pratt","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danica","family":"Wiredja","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus","family":"Toland","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6171-0688","authenticated-orcid":false,"given":"Daniel F","family":"Marker","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"2026062414274657200_nlag004-B1","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1126\/science.1164382","article-title":"An integrated genomic analysis of human glioblastoma multiforme","volume":"321","author":"Parsons","year":"2008","journal-title":"Science."},{"key":"2026062414274657200_nlag004-B2","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization classification of tumors of the central nervous system: a summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"2026062414274657200_nlag004-B3","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1056\/NEJMoa0808710","article-title":"IDH1 and IDH2 mutations in gliomas","volume":"360","author":"Yan","year":"2009","journal-title":"N Engl J Med."},{"key":"2026062414274657200_nlag004-B4","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1097\/PAS.0000000000002463","article-title":"A case of a fumarate hydratase deficient astrocytoma in association with a germline fumarate hydratase mutation with review of the literature: considerations for patients with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome","volume":"50","author":"Alfattal","year":"2026","journal-title":"Am J Surg Pathol."},{"key":"2026062414274657200_nlag004-B5","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/jnen\/nlae064","article-title":"FH-mutant glioma displaying the epigenetic signature of IDH-mutant astrocytomas","volume":"83","author":"Zschernack","year":"2024","journal-title":"J Neuropathol Exp Neurol."},{"key":"2026062414274657200_nlag004-B6","doi-asserted-by":"publisher","first-page":"nlaf086","DOI":"10.1093\/jnen\/nlaf086","article-title":"IDH-wildtype astrocytoma with FH mutation, epigenetic similarity to IDH-mutant astrocytoma, and hypermethylation of CDKN2A arising in the brainstem","author":"Smith","year":"2025","journal-title":"J Neuropathol Exp Neurol."},{"key":"2026062414274657200_nlag004-B7","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1093\/jnen\/nlae100","article-title":"Long survival in a patient with fumarate hydratase mutation-associated glioma","volume":"84","author":"Reimann","year":"2025","journal-title":"J Neuropathol Exp Neurol."},{"key":"2026062414274657200_nlag004-B8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/jnen\/nlac107","article-title":"Mutations of FH and IDH may induce gliomagenesis by similar mechanisms","volume":"82","author":"Raghunathan","year":"2022","journal-title":"J Neuropathol Exp Neurol."},{"key":"2026062414274657200_nlag004-B9","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.ccr.2010.03.017","article-title":"Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma","volume":"17","author":"Noushmehr","year":"2010","journal-title":"Cancer Cell."},{"key":"2026062414274657200_nlag004-B10","first-page":"e123","article-title":"SeSAMe: reducing artifactual detection of DNA methylation by infinium BeadChips in genomic deletions","volume":"46","author":"Zhou","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2026062414274657200_nlag004-B11","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/nature08617","article-title":"Cancer-associated IDH1 mutations produce 2-hydroxyglutarate","volume":"462","author":"Dang","year":"2009","journal-title":"Nature."},{"key":"2026062414274657200_nlag004-B12","doi-asserted-by":"crossref","first-page":"e690","DOI":"10.1371\/journal.pone.0000690","article-title":"The tricarboxylic acid cycle, an ancient metabolic network with a novel twist","volume":"2","author":"Mailloux","year":"2007","journal-title":"PLoS One."},{"key":"2026062414274657200_nlag004-B13","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1126\/science.1170944","article-title":"Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1\u03b1","volume":"324","author":"Zhao","year":"2009","journal-title":"Science."},{"key":"2026062414274657200_nlag004-B14","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.trecan.2020.12.011","article-title":"Roles and regulations of TET enzymes in solid tumors","volume":"7","author":"Bray","year":"2021","journal-title":"Trends Cancer."},{"key":"2026062414274657200_nlag004-B15","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/embor.2011.43","article-title":"The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases","volume":"12","author":"Chowdhury","year":"2011","journal-title":"EMBO Rep."},{"key":"2026062414274657200_nlag004-B16","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1042\/BST20190333","article-title":"Human 2-oxoglutarate-dependent oxygenases: nutrient sensors, stress responders, and disease mediators","volume":"48","author":"Fletcher","year":"2020","journal-title":"Biochem Soc Trans."},{"key":"2026062414274657200_nlag004-B17","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1136\/jclinpath-2011-200227","article-title":"Isocitrate dehydrogenase mutations in diffuse gliomas: clinical and aetiological implications","volume":"64","author":"Gupta","year":"2011","journal-title":"J Clin Pathol."},{"key":"2026062414274657200_nlag004-B18","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nature19081","article-title":"Tumour hypoxia causes DNA hypermethylation by reducing TET activity","volume":"537","author":"Thienpont","year":"2016","journal-title":"Nature."},{"key":"2026062414274657200_nlag004-B19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2006.03.005","article-title":"S-(2-Succinyl)cysteine: a novel chemical modification of tissue proteins by a krebs cycle intermediate","volume":"450","author":"Alderson","year":"2006","journal-title":"Arch Biochem Biophys."},{"key":"2026062414274657200_nlag004-B20","doi-asserted-by":"crossref","first-page":"110453","DOI":"10.1016\/j.celrep.2022.110453","article-title":"SDHB knockout and succinate accumulation are insufficient for tumorigenesis but dual SDHB\/NF1 loss yields SDHx-like pheochromocytomas","volume":"38","author":"Armstrong","year":"2022","journal-title":"Cell Rep."},{"key":"2026062414274657200_nlag004-B21","doi-asserted-by":"crossref","first-page":"4551","DOI":"10.1016\/j.celrep.2020.03.022","article-title":"TET-mediated hypermethylation primes SDH-deficient cells for HIF2\u03b1-driven mesenchymal transition","volume":"30","author":"Morin","year":"2020","journal-title":"Cell Rep."},{"key":"2026062414274657200_nlag004-B22","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1038\/modpathol.2013.86","article-title":"Succinate dehydrogenase deficiency is associated with decreased 5-hydroxymethylcytosine production in gastrointestinal stromal tumors: implications for mechanisms of tumorigenesis","volume":"26","author":"Mason","year":"2013","journal-title":"Mod Pathol."},{"key":"2026062414274657200_nlag004-B23","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40478-018-0544-y","article-title":"Network-based analysis of oligodendrogliomas predicts novel cancer gene candidates within the region of the 1p\/19q co-deletion","volume":"6","author":"Gladitz","year":"2018","journal-title":"Acta Neuropathol Commun."},{"key":"2026062414274657200_nlag004-B24","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3892\/ijo.2025.5779","article-title":"Knockdown of ACC1 promotes migration and invasion of U251 glioma cells by epigenetically suppressing SDH","volume":"67","author":"Wei","year":"2025","journal-title":"Int J Oncol."}],"container-title":["Journal of Neuropathology &amp; Experimental Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnen\/article-pdf\/85\/7\/789\/66753079\/nlag004.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnen\/article-pdf\/85\/7\/789\/66753079\/nlag004.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T18:27:55Z","timestamp":1782325675000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnen\/article\/85\/7\/789\/8460635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":24,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,2,4]]},"published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jnen\/nlag004","relation":{},"ISSN":["0022-3069","1554-6578"],"issn-type":[{"value":"0022-3069","type":"print"},{"value":"1554-6578","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,2,4]]}}}