{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:03:32Z","timestamp":1790075012353,"version":"4.0.1"},"reference-count":112,"publisher":"Bioscientifica","issue":"6","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,10]]},"abstract":"<jats:p>\n                    Metabolites represent the highest layer of biological information. Their diverse chemical nature enables networks of chemical reactions that are critical for maintaining life by providing energy and building blocks. Quantification by targeted and untargeted analytical methods using either mass spectrometry or nuclear magnetic resonance spectroscopy has been applied to pheochromocytoma\/paraganglioma (PPGL) with the long-term goal to improve diagnosis and therapy. PPGLs have unique features that provide useful biomarkers and clues for targeted treatments. First, high production rates of catecholamines and metanephrines allow for specific and sensitive detection of the disease in plasma or urine. Secondly, PPGLs are associated with heritable pathogenic variants (PVs) in around 40% of cases, many of which occur in genes encoding enzymes, such as succinate dehydrogenase (SDH) and fumarate hydratase (FH). These genetic aberrations lead to the overproduction of oncometabolites succinate or fumarate, respectively, and are detectable in tumors and blood. Such metabolic dysregulation can be exploited diagnostically, with the aim to ensure appropriate interpretation of gene variants, especially those with unknown significance, and facilitate early tumor detection through regular patient follow-up. Furthermore,\n                    <jats:italic>SDHx<\/jats:italic>\n                    and\n                    <jats:italic>FH<\/jats:italic>\n                    PV alter cellular pathways, including DNA hypermethylation, hypoxia signaling, redox homeostasis, DNA repair, calcium signaling, kinase cascades, and central carbon metabolism. Pharmacological interventions targeted toward such features have the potential to uncover treatments against metastatic PPGL, around 50% of which are associated with germline PV in\n                    <jats:italic>SDHx<\/jats:italic>\n                    . With the availability of omics technologies for all layers of biological information, personalized diagnostics and treatment is in close reach.\n                  <\/jats:p>","DOI":"10.1530\/erc-22-0376","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T09:52:20Z","timestamp":1678441940000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":12,"title":["Metabolomics in paraganglioma: applications and perspectives from genetics to therapy"],"prefix":"10.1530","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-2477","authenticated-orcid":true,"given":"Susan","family":"Richter","sequence":"first","affiliation":[{"name":"Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universit\u00e4t Dresden, Fetscherstrasse, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J","family":"Garrett","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6932-333X","authenticated-orcid":true,"given":"Nicole","family":"Bechmann","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universit\u00e4t Dresden, Fetscherstrasse, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-0368","authenticated-orcid":true,"given":"Roderick J","family":"Clifton-Bligh","sequence":"additional","affiliation":[{"name":"Cancer Genetics Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St Leonards, Australia"},{"name":"Department of Endocrinology, Royal North Shore Hospital, St Leonards, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans K","family":"Ghayee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, University of Florida College of Medicine and Malcom Randall VA Medical Center, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"American Journal of Human Genetics","first-page":"151","article-title":"Mutations in MDH2, encoding a Krebs cycle enzyme, cause early-onset severe encephalopathy","volume":"100","author":"Ait-El-Mkadem","year":"2017","unstructured":"Ait-El-Mkadem SDayem-Quere MGusic MChaussenot ABannwarth SFrancois BGenin ECFragaki KVolker-Touw CLMVasnier C, 2017Mutations in MDH2, encoding a Krebs cycle enzyme, cause early-onset severe encephalopathy. American Journal of Human Genetics100151\u2013159. (https:\/\/doi.org\/10.1016\/j.ajhg.2016.11.014)"},{"key":"bib2","series-title":"Nature Methods","first-page":"747","article-title":"Mass spectrometry-based metabolomics: a guide for annotation, quantification and best reporting practices","volume":"18","author":"Alseekh","year":"2021","unstructured":"Alseekh SAharoni ABrotman YContrepois KD\u2019auria JEwald JC Ewald JFraser PDGiavalisco PHall RD, 2021Mass spectrometry-based metabolomics: a guide for annotation, quantification and best reporting practices. Nature Methods18747\u2013756. (https:\/\/doi.org\/10.1038\/s41592-021-01197-1)"},{"key":"bib3","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"2539","article-title":"Fumarate hydratase is a novel gene for familial non-medullary thyroid cancer","volume":"107","author":"Alzahrani","year":"2022","unstructured":"Alzahrani ASAlswailem MAlghamdi B & Al-Hindi H2022Fumarate hydratase is a novel gene for familial non-medullary thyroid cancer. Journal of Clinical Endocrinology and Metabolism1072539\u20132544. (https:\/\/doi.org\/10.1210\/clinem\/dgac386)"},{"key":"bib4","series-title":"Nature Reviews. Endocrinology","first-page":"435","article-title":"International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers","volume":"17","author":"Amar","year":"2021","unstructured":"Amar LPacak KSteichen OAkker SAAylwin SJBBaudin EBuffet ABurnichon NClifton-Bligh RJDahia PLM, 2021International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers. Nature Reviews. Endocrinology17435\u2013444. (https:\/\/doi.org\/10.1038\/s41574-021-00492-3)"},{"key":"bib5","series-title":"Annals of Oncology","article-title":"567O First International Randomized Study in Malignant Progressive pheochromocytoma and paragangliomas (FIRSTMAPPP): an academic double-blind trial investigating sunitinib","volume":"32","author":"Baudin","year":"2021","unstructured":"Baudin EGoichot BBerruti AHadoux JMoalla SLaboureau SNoelting SDe La Fouchardi\u00e8re CKienitz TDeutschbein T, 2021567O First International Randomized Study in Malignant Progressive pheochromocytoma and paragangliomas (FIRSTMAPPP): an academic double-blind trial investigating sunitinib. Annals of Oncology32 S621. (https:\/\/doi.org\/10.1016\/j.annonc.2021.08.702)"},{"key":"bib6","series-title":"Endocrine-Related Cancer","first-page":"625","article-title":"HIF2alpha supports pro-metastatic behavior in pheochromocytomas\/paragangliomas","volume":"27","author":"Bechmann","year":"2020","unstructured":"Bechmann NMoskopp MLUllrich MCalsina BWallace PWRichter SFriedemann MLangton KFliedner SMJTimmers HJLM, 2020HIF2alpha supports pro-metastatic behavior in pheochromocytomas\/paragangliomas. Endocrine-Related Cancer27625\u2013640. (https:\/\/doi.org\/10.1530\/ERC-20-0205)"},{"key":"bib7","series-title":"Hormone and Metabolic Research","first-page":"326","article-title":"Adrenal hormone interactions and metabolism: a single sample multi-omics approach","volume":"53","author":"Bechmann","year":"2021","unstructured":"Bechmann NWatts DSteenblock CWallace PWSchurmann ABornstein SRWielockx BEisenhofer G & Peitzsch M2021Adrenal hormone interactions and metabolism: a single sample multi-omics approach. Hormone and Metabolic Research53326\u2013334. (https:\/\/doi.org\/10.1055\/a-1440-0278)"},{"key":"bib8","series-title":"Metabolites","article-title":"Preanalytical pitfalls in untargeted plasma nuclear magnetic resonance metabolomics of endocrine hypertension","volume":"12","author":"Bliziotis","year":"2022","unstructured":"Bliziotis NGKluijtmans LAJTinnevelt GHReel PReel SLangton KRobledo MPamporaki CPecori AVan Kralingen J, 2022Preanalytical pitfalls in untargeted plasma nuclear magnetic resonance metabolomics of endocrine hypertension. Metabolites12. (https:\/\/doi.org\/10.3390\/metabo12080679)"},{"key":"bib9","series-title":"Nature Cell Biology","first-page":"1317","article-title":"Pyruvate carboxylation enables growth of SDH-deficient cells by supporting aspartate biosynthesis","volume":"17","author":"Cardaci","year":"2015","unstructured":"Cardaci SZheng LMackay GVan Den Broek NJMackenzie EDNixon CStevenson DTumanov SBulusu VKamphorst JJ, 2015Pyruvate carboxylation enables growth of SDH-deficient cells by supporting aspartate biosynthesis. Nature Cell Biology171317\u20131326. (https:\/\/doi.org\/10.1038\/ncb3233)"},{"key":"bib10","series-title":"Journal of the National Cancer Institute","article-title":"Whole-exome sequencing identifies MDH2 as a new familial paraganglioma gene","volume":"107","author":"Cascon","year":"2015","unstructured":"Cascon AComino-Mendez ICurras-Freixes MDe Cubas AAContreras LRichter SPeitzsch MMancikova VInglada-Perez LPerez-Barrios A, 2015Whole-exome sequencing identifies MDH2 as a new familial paraganglioma gene. Journal of the National Cancer Institute107djv053. (https:\/\/doi.org\/10.1093\/jnci\/djv053)"},{"key":"bib11","series-title":"Human Molecular Genetics","first-page":"2440","article-title":"Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas","volume":"23","author":"Castro-Vega","year":"2014","unstructured":"Castro-Vega LJBuffet ADe Cubas AACascon AMenara MKhalifa EAmar LAzriel SBourdeau IChabre O, 2014Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Human Molecular Genetics232440\u20132446. (https:\/\/doi.org\/10.1093\/hmg\/ddt639)"},{"key":"bib12","series-title":"Journal of Biological Chemistry","first-page":"25130","article-title":"Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing","volume":"275","author":"Chandel","year":"2000","unstructured":"Chandel NSMcclintock DSFeliciano CEWood TMMelendez JARodriguez AM & Schumacker PT2000Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. Journal of Biological Chemistry27525130\u201325138. (https:\/\/doi.org\/10.1074\/jbc.M001914200)"},{"key":"bib13","series-title":"American Journal of Surgical Pathology","first-page":"627","article-title":"Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry","volume":"38","author":"Chen","year":"2014","unstructured":"Chen YBBrannon ARToubaji ADudas MEWon HHAl-Ahmadie HAFine SWGopalan AFrizzell NVoss MH, 2014Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry. American Journal of Surgical Pathology38627\u2013637. (https:\/\/doi.org\/10.1097\/PAS.0000000000000163)"},{"key":"bib14","series-title":"Molecular and Cellular Proteomics","first-page":"1453","article-title":"Simultaneous metabolite, protein, lipid extraction (Simplex): a combinatorial multimolecular omics approach for systems biology","volume":"15","author":"Coman","year":"2016","unstructured":"Coman CSolari FAHentschel ASickmann AZahedi RP & Ahrends R2016Simultaneous metabolite, protein, lipid extraction (Simplex): a combinatorial multimolecular omics approach for systems biology. Molecular and Cellular Proteomics151453\u20131466. (https:\/\/doi.org\/10.1074\/mcp.M115.053702)"},{"key":"bib15","series-title":"Journal of Molecular Diagnostics","first-page":"575","article-title":"PheoSeq: a targeted next-generation sequencing assay for pheochromocytoma and paraganglioma diagnostics","volume":"19","author":"Curras-Freixes","year":"2017","unstructured":"Curras-Freixes MPineiro-Yanez EMontero-Conde CApellaniz-Ruiz MCalsina BMancikova VRemacha LRichter SErcolino TRogowski-Lehmann N, 2017PheoSeq: a targeted next-generation sequencing assay for pheochromocytoma and paraganglioma diagnostics. Journal of Molecular Diagnostics19575\u2013588. (https:\/\/doi.org\/10.1016\/j.jmoldx.2017.04.009)"},{"key":"bib16","series-title":"Annals of Oncology","first-page":"599","article-title":"IDH mutations in cancer and progress toward development of targeted therapeutics","volume":"27","author":"Dang","year":"2016","unstructured":"Dang LYen K & Attar EC2016IDH mutations in cancer and progress toward development of targeted therapeutics. Annals of Oncology27599\u2013608. (https:\/\/doi.org\/10.1093\/annonc\/mdw013)"},{"key":"bib17","series-title":"Journal of Clinical Endocrinology and Metabolism","article-title":"Surveillance improves outcomes for carriers of SDHB pathogenic variants: a multicenter study","volume":"107","author":"Davidoff","year":"2022","unstructured":"Davidoff DFBenn DEField MCrook ARobinson BGTucker KDe Abreu Lourenco RBurgess JR & Clifton-Bligh RJ2022Surveillance improves outcomes for carriers of SDHB pathogenic variants: a multicenter study. Journal of Clinical Endocrinology and Metabolism107 e1907\u2013e1916. (https:\/\/doi.org\/10.1210\/clinem\/dgac019)"},{"key":"bib18","series-title":"npj Digital Medicine","article-title":"Guidelines and quality criteria for artificial intelligence-based prediction models in healthcare: a scoping review","volume":"5","author":"de Hond","year":"2022","unstructured":"de Hond AAHLeeuwenberg AMHooft LKant IMJNijman SWJVan Os HJAAardoom JJDebray TPASchuit EVan Smeden M, 2022Guidelines and quality criteria for artificial intelligence-based prediction models in healthcare: a scoping review. npj Digital Medicine5 2. (https:\/\/doi.org\/10.1038\/s41746-021-00549-7)"},{"key":"bib19","series-title":"Clinical Biochemist. Reviews","first-page":"69","article-title":"Metabologenomics of phaeochromocytoma and paraganglioma: an integrated approach for personalised biochemical and genetic testing","volume":"38","author":"Eisenhofer","year":"2017","unstructured":"Eisenhofer GKlink BRichter SLenders JW & Robledo M2017Metabologenomics of phaeochromocytoma and paraganglioma: an integrated approach for personalised biochemical and genetic testing. Clinical Biochemist. Reviews3869\u2013100."},{"key":"bib20","series-title":"Pharmacological Reviews","first-page":"331","article-title":"Catecholamine metabolism: a contemporary view with implications for physiology and medicine","volume":"56","author":"Eisenhofer","year":"2004","unstructured":"Eisenhofer GKopin IJ & Goldstein DS2004Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacological Reviews56331\u2013349. (https:\/\/doi.org\/10.1124\/pr.56.3.1)"},{"key":"bib21","series-title":"European Journal of Cancer","first-page":"1739","article-title":"Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status","volume":"48","author":"Eisenhofer","year":"2012","unstructured":"Eisenhofer GLenders JWSiegert GBornstein SRFriberg PMilosevic DMannelli MLinehan WMAdams KTimmers HJ, 2012Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status. European Journal of Cancer481739\u20131749. (https:\/\/doi.org\/10.1016\/j.ejca.2011.07.016)"},{"key":"bib22","series-title":"Clinical Chemistry","first-page":"1486","article-title":"Laboratory evaluation of pheochromocytoma and paraganglioma","volume":"60","author":"Eisenhofer","year":"2014","unstructured":"Eisenhofer G & Peitzsch M2014Laboratory evaluation of pheochromocytoma and paraganglioma. Clinical Chemistry601486\u20131499. (https:\/\/doi.org\/10.1373\/clinchem.2014.224832)"},{"key":"bib23","series-title":"European Journal of Endocrinology","first-page":"647","article-title":"Metabolic impact of pheochromocytoma\/paraganglioma: targeted metabolomics in patients before and after tumor removal","volume":"181","author":"Erlic","year":"2019","unstructured":"Erlic ZKurlbaum MDeutschbein TNolting SPrejbisz ATimmers HRichter SPrehn CWeismann DAdamski J, 2019Metabolic impact of pheochromocytoma\/paraganglioma: targeted metabolomics in patients before and after tumor removal. European Journal of Endocrinology181647\u2013657. (https:\/\/doi.org\/10.1530\/EJE-19-0589)"},{"key":"bib24","series-title":"Cancer Cell","first-page":"181","article-title":"Comprehensive molecular characterization of pheochromocytoma and paraganglioma","volume":"31","author":"Fishbein","year":"2017","unstructured":"Fishbein LLeshchiner IWalter VDanilova LRobertson AGJohnson ARLichtenberg TMMurray BAGhayee HKElse T, 2017Comprehensive molecular characterization of pheochromocytoma and paraganglioma. Cancer Cell31181\u2013193. (https:\/\/doi.org\/10.1016\/j.ccell.2017.01.001)"},{"key":"bib25","series-title":"Scientific Reports","article-title":"Effects of dichloroacetate as single agent or in combination with GW6471 and metformin in paraganglioma cells","volume":"8","author":"Florio","year":"2018","unstructured":"Florio RDe Lellis LVeschi SVerginelli FDi Giacomo VGallorini MPerconti SSanna MMariani-Costantini RNatale A, 2018Effects of dichloroacetate as single agent or in combination with GW6471 and metformin in paraganglioma cells. Scientific Reports8 13610. (https:\/\/doi.org\/10.1038\/s41598-018-31797-5)"},{"key":"bib26","series-title":"Nature","first-page":"225","article-title":"Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase","volume":"477","author":"Frezza","year":"2011","unstructured":"Frezza CZheng LFolger ORajagopalan KNMackenzie EDJerby LMicaroni MChaneton BAdam JHedley A, 2011Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature477225\u2013228. (https:\/\/doi.org\/10.1038\/nature10363)"},{"key":"bib27","series-title":"Genetics in Medicine","first-page":"41","article-title":"Quantifying evidence toward pathogenicity for rare phenotypes: the case of succinate dehydrogenase genes, SDHB and SDHD","volume":"24","author":"Garrett","year":"2022","unstructured":"Garrett ALoveday CKing LButler SRobinson RHorton CYussuf AChoi STorr BDurkie M, 2022Quantifying evidence toward pathogenicity for rare phenotypes: the case of succinate dehydrogenase genes, SDHB and SDHD. Genetics in Medicine2441\u201350. (https:\/\/doi.org\/10.1016\/j.gim.2021.08.004)"},{"key":"bib28","series-title":"Cancer Research","first-page":"5615","article-title":"Mutations in the SDHB gene are associated with extra-adrenal and\/or malignant phaeochromocytomas","volume":"63","author":"Gimenez-Roqueplo","year":"2003","unstructured":"Gimenez-Roqueplo APFavier JRustin PRieubland CCrespin MNau VKhau Van Kien PCorvol PPlouin PFJeunemaitre X, 2003Mutations in the SDHB gene are associated with extra-adrenal and\/or malignant phaeochromocytomas. Cancer Research635615\u20135621."},{"key":"bib29","series-title":"Cancer Research","first-page":"3480","article-title":"Loss of SDHB promotes dysregulated iron homeostasis, oxidative stress, and sensitivity to ascorbate","volume":"81","author":"Goncalves","year":"2021","unstructured":"Goncalves JMoog SMorin AGentric GMuller SMorrell APKluckova KStewart TJAndoniadou CLLussey-Lepoutre C, 2021Loss of SDHB promotes dysregulated iron homeostasis, oxidative stress, and sensitivity to ascorbate. Cancer Research813480\u20133494. (https:\/\/doi.org\/10.1158\/0008-5472.CAN-20-2936)"},{"key":"bib30","series-title":"Cell Reports","article-title":"Genetic impairment of succinate metabolism disrupts bioenergetic sensing in adrenal neuroendocrine cancer","volume":"40","author":"Gupta","year":"2022","unstructured":"Gupta PStrange KTelange RGuo AHatch HSobh AElie JCarter AMTotenhagen JTan C, 2022Genetic impairment of succinate metabolism disrupts bioenergetic sensing in adrenal neuroendocrine cancer. Cell Reports40 111218. (https:\/\/doi.org\/10.1016\/j.celrep.2022.111218)"},{"key":"bib31","series-title":"Molecular and Cellular Biology","first-page":"718","article-title":"Loss of the SdhB, but not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis","volume":"28","author":"Guzy","year":"2008","unstructured":"Guzy RDSharma BBell EChandel NS & Schumacker PT2008Loss of the SdhB, but not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Molecular and Cellular Biology28718\u2013731. (https:\/\/doi.org\/10.1128\/MCB.01338-07)"},{"key":"bib32","series-title":"International Journal of Cancer","first-page":"2711","article-title":"SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma","volume":"135","author":"Hadoux","year":"2014","unstructured":"Hadoux JFavier JScoazec JYLeboulleux SAl Ghuzlan ACaramella CD\u00e9andreis DBorget ILoriot CChougnet C, 2014SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma. International Journal of Cancer1352711\u20132720. (https:\/\/doi.org\/10.1002\/ijc.28913)"},{"key":"bib33","series-title":"Journal of the National Cancer Institute","first-page":"130","article-title":"Germline SUCLG2 variants in patients with pheochromocytoma and paraganglioma","volume":"114","author":"Hadrava Vanova","year":"2022","unstructured":"Hadrava Vanova KPang YKrobova LKraus MNahacka ZBoukalova SPack SDZobalova RZhu JHuynh TT, 2022Germline SUCLG2 variants in patients with pheochromocytoma and paraganglioma. Journal of the National Cancer Institute114130\u2013138. (https:\/\/doi.org\/10.1093\/jnci\/djab158)"},{"key":"bib34","series-title":"Clinical Cancer Research","first-page":"684","article-title":"Phase I study of N(1),N(11)-diethylnorspermine in patients with non-small cell lung cancer","volume":"8","author":"Hahm","year":"2002","unstructured":"Hahm HAEttinger DSBowling KHoker BChen TLZabelina Y & Casero RA2002Phase I study of N(1),N(11)-diethylnorspermine in patients with non-small cell lung cancer. Clinical Cancer Research8684\u2013690."},{"key":"bib35","series-title":"British Journal of Cancer","first-page":"1855","article-title":"Global metabolomic profiling of uterine leiomyomas","volume":"117","author":"Heinonen","year":"2017","unstructured":"Heinonen HRMehine MMakinen NPasanen APitkanen EKarhu ASarvilinna NSSjoberg JHeikinheimo OButzow R, 2017Global metabolomic profiling of uterine leiomyomas. British Journal of Cancer1171855\u20131864. (https:\/\/doi.org\/10.1038\/bjc.2017.361)"},{"key":"bib37","series-title":"PLoS One","article-title":"A new specific succinate-glutamate metabolomic hallmark in sdhx-related paragangliomas","volume":"8","author":"Imperiale","year":"2013","unstructured":"Imperiale AMoussallieh FMSebag FBrunaud LBarlier AElbayed KBachellier PGoichot BPacak KNamer IJ, 2013A new specific succinate-glutamate metabolomic hallmark in sdhx-related paragangliomas. PLoS One8 e80539. (https:\/\/doi.org\/10.1371\/journal.pone.0080539)"},{"key":"bib36","series-title":"Neoplasia","first-page":"55","article-title":"Metabolome profiling by HRMAS NMR spectroscopy of pheochromocytomas and paragangliomas detects SDH deficiency: clinical and pathophysiological implications","volume":"17","author":"Imperiale","year":"2015","unstructured":"Imperiale AMoussallieh FMRoche PBattini SCicek AESebag FBrunaud LBarlier AElbayed KLoundou A, 2015Metabolome profiling by HRMAS NMR spectroscopy of pheochromocytomas and paragangliomas detects SDH deficiency: clinical and pathophysiological implications. Neoplasia1755\u201365. (https:\/\/doi.org\/10.1016\/j.neo.2014.10.010)"},{"key":"bib38","series-title":"PNAS","first-page":"314","article-title":"Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations","volume":"108","author":"Janeway","year":"2011","unstructured":"Janeway KAKim SYLodish MNos\u00e9 VRustin PGaal JDahia PLLiegl BBall ERRaygada M, 2011Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. PNAS108314\u2013318. (https:\/\/doi.org\/10.1073\/pnas.1009199108)"},{"key":"bib39","series-title":"Head and Neck","first-page":"2088","article-title":"Feasibility of a wait-and-scan period as initial management strategy for head and neck paraganglioma","volume":"39","author":"Jansen","year":"2017","unstructured":"Jansen TTGTimmers HJLMMarres HAM & Kunst HPM2017Feasibility of a wait-and-scan period as initial management strategy for head and neck paraganglioma. Head and Neck392088\u20132094. (https:\/\/doi.org\/10.1002\/hed.24871)"},{"key":"bib40","series-title":"Cellular and Molecular Neurobiology","first-page":"1099","article-title":"Continued tumor reduction of metastatic pheochromocytoma\/paraganglioma harboring succinate dehydrogenase Subunit B mutations with cyclical chemotherapy","volume":"38","author":"Jawed","year":"2018","unstructured":"Jawed IVelarde MDarr RWolf KIAdams KVenkatesan AMBalasubramaniam SPoruchynsky MSReynolds JCPacak K, 2018Continued tumor reduction of metastatic pheochromocytoma\/paraganglioma harboring succinate dehydrogenase Subunit B mutations with cyclical chemotherapy. Cellular and Molecular Neurobiology381099\u20131106. (https:\/\/doi.org\/10.1007\/s10571-018-0579-4)"},{"key":"bib41","series-title":"Cancers (Basel)","article-title":"New insights on the genetics of pheochromocytoma and paraganglioma and its clinical implications","volume":"14","author":"Jhawar","year":"2022","unstructured":"Jhawar SArakawa YKumar SVarghese DKim YSRoper NElloumi FPommier YPacak K & Del Rivero J2022New insights on the genetics of pheochromocytoma and paraganglioma and its clinical implications. Cancers (Basel)14594. (https:\/\/doi.org\/10.3390\/cancers14030594)"},{"key":"bib42","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"5","article-title":"Rationale and evidence for sunitinib in the treatment of malignant paraganglioma\/pheochromocytoma","volume":"94","author":"Joshua","year":"2009","unstructured":"Joshua AMEzzat SAsa SLEvans ABroom RFreeman M & Knox JJ2009Rationale and evidence for sunitinib in the treatment of malignant paraganglioma\/pheochromocytoma. Journal of Clinical Endocrinology and Metabolism945\u20139. (https:\/\/doi.org\/10.1210\/jc.2008-1836)"},{"key":"bib43","series-title":"New England Journal of Medicine","first-page":"2059","article-title":"Belzutifan, a potent HIF2alpha inhibitor, in the Pacak-Zhuang syndrome","volume":"385","author":"Kamihara","year":"2021","unstructured":"Kamihara JHamilton KVPollard JAClinton CMMadden JALin JImamovic AWall CBWassner AJWeil BR, 2021Belzutifan, a potent HIF2alpha inhibitor, in the Pacak-Zhuang syndrome. New England Journal of Medicine3852059\u20132065. (https:\/\/doi.org\/10.1056\/NEJMoa2110051)"},{"key":"bib44","series-title":"Frontiers in Genetics","article-title":"Three-in-one simultaneous extraction of proteins, metabolites and lipids for multi-omics","volume":"12","author":"Kang","year":"2021","unstructured":"Kang JDavid LLi YCang J & Chen S2021Three-in-one simultaneous extraction of proteins, metabolites and lipids for multi-omics. Frontiers in Genetics12 635971. (https:\/\/doi.org\/10.3389\/fgene.2021.635971)"},{"key":"bib45","series-title":"Biochimica et Biophysica Acta. Reviews on Cancer","article-title":"Oncometabolites lactate and succinate drive pro-angiogenic macrophage response in tumors","volume":"1874","author":"Kes","year":"2020","unstructured":"Kes MMGVan Den Bossche JGriffioen AW & Huijbers EJM2020Oncometabolites lactate and succinate drive pro-angiogenic macrophage response in tumors. Biochimica et Biophysica Acta. Reviews on Cancer1874 188427. (https:\/\/doi.org\/10.1016\/j.bbcan.2020.188427)"},{"key":"bib46","series-title":"Science Translational Medicine","article-title":"Recurrent epimutation of SDHC in gastrointestinal stromal tumors","volume":"6","author":"Killian","year":"2014","unstructured":"Killian JKMiettinen MWalker RLWang YZhu YJWaterfall JJNoyes NRetnakumar PYang ZSmith WI, 2014Recurrent epimutation of SDHC in gastrointestinal stromal tumors. Science Translational Medicine6 268ra177. (https:\/\/doi.org\/10.1126\/scitranslmed.3009961)"},{"key":"bib47","series-title":"Molecular Genetics and Metabolism Reports","first-page":"45","article-title":"Utility of the succinate: fumarate ratio for assessing SDH dysfunction in different tumor types","volume":"10","author":"Kim","year":"2017","unstructured":"Kim EWright MJSioson LNovos TGill AJBenn DEWhite CDwight T & Clifton-Bligh RJ2017Utility of the succinate: fumarate ratio for assessing SDH dysfunction in different tumor types. Molecular Genetics and Metabolism Reports1045\u201349. (https:\/\/doi.org\/10.1016\/j.ymgmr.2016.12.006)"},{"key":"bib48","series-title":"FASEB Journal","first-page":"303","article-title":"Succinate dehydrogenase deficiency in a chromaffin cell model retains metabolic fitness through the maintenance of mitochondrial NADH oxidoreductase function","volume":"34","author":"Kluckova","year":"2020","unstructured":"Kluckova KThakker AVettore LEscribano-Gonzalez CHindshaw RLTearle JLEGoncalves JKaul BLavery GGFavier J, 2020Succinate dehydrogenase deficiency in a chromaffin cell model retains metabolic fitness through the maintenance of mitochondrial NADH oxidoreductase function. FASEB Journal34303\u2013315. (https:\/\/doi.org\/10.1096\/fj.201901456R)"},{"key":"bib49","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"2801","article-title":"Succinate: a serum biomarker of SDHB mutated paragangliomas and pheochromocytomas","volume":"107","author":"Lamy","year":"2022","unstructured":"Lamy CTissot HFaron MBaudin ELamartina LPradon CAl Ghuzlan ALeboulleux SPerfettini JLPaci A, 2022Succinate: a serum biomarker of SDHB mutated paragangliomas and pheochromocytomas. Journal of Clinical Endocrinology and Metabolism1072801\u20132810. (https:\/\/doi.org\/10.1210\/clinem\/dgac474)"},{"key":"bib50","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"1915","article-title":"Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline","volume":"99","author":"Lenders","year":"2014","unstructured":"Lenders JWDuh QYEisenhofer GGimenez-Roqueplo APGrebe SKMurad MHNaruse MPacak KYoung WF & Endocrine Society2014Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism991915\u20131942. (https:\/\/doi.org\/10.1210\/jc.2014-1498)"},{"key":"bib51","series-title":"Endocrinology","first-page":"27","article-title":"Succinate-to-fumarate ratio as a new metabolic marker to detect the presence of SDHB\/D-related paraganglioma: initial experimental and ex vivo findings","volume":"155","author":"Lendvai","year":"2014","unstructured":"Lendvai NPawlosky RBullova PEisenhofer GPatocs AVeech RL & Pacak K2014Succinate-to-fumarate ratio as a new metabolic marker to detect the presence of SDHB\/D-related paraganglioma: initial experimental and ex vivo findings. Endocrinology15527\u201332. (https:\/\/doi.org\/10.1210\/en.2013-1549)"},{"key":"bib52","series-title":"Cancer Cell","first-page":"739","article-title":"SDH mutations establish a hypermethylator phenotype in paraganglioma","volume":"23","author":"Letouze","year":"2013","unstructured":"Letouze EMartinelli CLoriot CBurnichon NAbermil NOttolenghi CJanin MMenara MNguyen ATBenit P, 2013SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell23739\u2013752. (https:\/\/doi.org\/10.1016\/j.ccr.2013.04.018)"},{"key":"bib53","series-title":"Journal of Proteome Research","first-page":"3039","article-title":"Simultaneous extraction of RNA and metabolites from single kidney tissue specimens for combined transcriptomic and metabolomic profiling","volume":"17","author":"Leuthold","year":"2018","unstructured":"Leuthold PSchwab MHofmann UWinter SRausch SPollak MNHennenlotter JBedke JSchaeffeler E & Haag M2018Simultaneous extraction of RNA and metabolites from single kidney tissue specimens for combined transcriptomic and metabolomic profiling. Journal of Proteome Research173039\u20133049. (https:\/\/doi.org\/10.1021\/acs.jproteome.8b00199)"},{"key":"bib54","series-title":"Molecular Cell","first-page":"661","article-title":"NADP(+)-IDH mutations promote Hypersuccinylation that impairs mitochondria respiration and induces apoptosis resistance","volume":"60","author":"Li","year":"2015","unstructured":"Li FHe XYe DLin YYu HYao CHuang LZhang JWang FXu S, 2015NADP(+)-IDH mutations promote Hypersuccinylation that impairs mitochondria respiration and induces apoptosis resistance. Molecular Cell60661\u2013675. (https:\/\/doi.org\/10.1016\/j.molcel.2015.10.017)"},{"key":"bib55","series-title":"Journal of Clinical Endocrinology and Metabolism","article-title":"Somatic IDH1 hotspot variants in Chinese patients with pheochromocytomas and paragangliomas","volume":"2022","author":"Li","year":"2022","unstructured":"Li MHe YPang YZhang JFeng YHe YXu XWei YZhong DDeng W, 2022Somatic IDH1 hotspot variants in Chinese patients with pheochromocytomas and paragangliomas. Journal of Clinical Endocrinology and Metabolism2022dgac653. (https:\/\/doi.org\/10.1210\/clinem\/dgac653)"},{"key":"bib56","series-title":"Current Opinion in Cell Biology","first-page":"144","article-title":"Advances into understanding metabolites as signaling molecules in cancer progression","volume":"63","author":"Liu","year":"2020","unstructured":"Liu JY & Wellen KE2020Advances into understanding metabolites as signaling molecules in cancer progression. Current Opinion in Cell Biology63144\u2013153. (https:\/\/doi.org\/10.1016\/j.ceb.2020.01.013)"},{"key":"bib57","series-title":"Cancers (Basel)","article-title":"Targeting NRF2-governed glutathione synthesis for SDHB-mutated pheochromocytoma and paraganglioma","volume":"12","author":"Liu","year":"2020a","unstructured":"Liu YPang YCaisova VDing JYu DZhou YHuynh TTGhayee HPacak K & Yang C2020aTargeting NRF2-governed glutathione synthesis for SDHB-mutated pheochromocytoma and paraganglioma. Cancers (Basel)12280. (https:\/\/doi.org\/10.3390\/cancers12020280)"},{"key":"bib58","series-title":"Clinical Cancer Research","first-page":"3868","article-title":"Therapeutic targeting of SDHB-mutated pheochromocytoma\/paraganglioma with pharmacologic ascorbic acid","volume":"26","author":"Liu","year":"2020b","unstructured":"Liu YPang YZhu BUher OCaisova VHuynh TTTaieb DHadrava Vanova KGhayee HKNeuzil J, 2020bTherapeutic targeting of SDHB-mutated pheochromocytoma\/paraganglioma with pharmacologic ascorbic acid. Clinical Cancer Research263868\u20133880. (https:\/\/doi.org\/10.1158\/1078-0432.CCR-19-2335)"},{"key":"bib59","series-title":"Metabolic Engineering","first-page":"187","article-title":"Dual loss of succinate dehydrogenase (SDH) and complex I activity is necessary to recapitulate the metabolic phenotype of SDH mutant tumors","volume":"43","author":"Lorendeau","year":"2017","unstructured":"Lorendeau DRinaldi GBoon RSpincemaille PMetzger KJager CChristen SDong XKuenen SVoordeckers K, 2017Dual loss of succinate dehydrogenase (SDH) and complex I activity is necessary to recapitulate the metabolic phenotype of SDH mutant tumors. Metabolic Engineering43187\u2013197. (https:\/\/doi.org\/10.1016\/j.ymben.2016.11.005)"},{"key":"bib62","series-title":"Nature Communications","article-title":"Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism","volume":"6","author":"Lussey-Lepoutre","year":"2015","unstructured":"Lussey-Lepoutre CHollinshead KELudwig CMenara MMorin ACastro-Vega LJParker SJJanin MMartinelli COttolenghi C, 2015Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism. Nature Communications6 8784. (https:\/\/doi.org\/10.1038\/ncomms9784)"},{"key":"bib61","series-title":"Clinical Cancer Research","first-page":"1120","article-title":"In vivo detection of succinate by magnetic resonance spectroscopy as a hallmark of SDHx mutations in paraganglioma","volume":"22","author":"Lussey-Lepoutre","year":"2016","unstructured":"Lussey-Lepoutre CBellucci AMorin ABuffet AAmar LJanin MOttolenghi CZinzindohoue FAutret GBurnichon N, 2016In vivo detection of succinate by magnetic resonance spectroscopy as a hallmark of SDHx mutations in paraganglioma. Clinical Cancer Research221120\u20131129. (https:\/\/doi.org\/10.1158\/1078-0432.CCR-15-1576)"},{"key":"bib60","series-title":"European Journal of Nuclear Medicine and Molecular Imaging","first-page":"1510","article-title":"Succinate detection using in vivo (1)H-MR spectroscopy identifies germline and somatic SDHx mutations in paragangliomas","volume":"47","author":"Lussey-Lepoutre","year":"2020","unstructured":"Lussey-Lepoutre CBellucci ABurnichon NAmar LBuffet ADrossart TFontaine SClement OBenit PRustin P, 2020Succinate detection using in vivo (1)H-MR spectroscopy identifies germline and somatic SDHx mutations in paragangliomas. European Journal of Nuclear Medicine and Molecular Imaging471510\u20131517. (https:\/\/doi.org\/10.1007\/s00259-019-04633-9)"},{"key":"bib63","series-title":"Current Opinion in Biotechnology","first-page":"34","article-title":"The future of NMR-based metabolomics","volume":"43","author":"Markley","year":"2017","unstructured":"Markley JLBruschweiler REdison ASEghbalnia HRPowers RRaftery D & Wishart DS2017The future of NMR-based metabolomics. Current Opinion in Biotechnology4334\u201340. (https:\/\/doi.org\/10.1016\/j.copbio.2016.08.001)"},{"key":"bib64","series-title":"Cancers (Basel)","article-title":"Metformin treatment induces different response in pheochromocytoma\/paraganglioma tumour cells and in primary fibroblasts","volume":"14","author":"Martinelli","year":"2022","unstructured":"Martinelli SAmore FMello TMannelli MMaggi M & Rapizzi E2022Metformin treatment induces different response in pheochromocytoma\/paraganglioma tumour cells and in primary fibroblasts. Cancers (Basel)143471. (https:\/\/doi.org\/10.3390\/cancers14143471)"},{"key":"bib65","series-title":"Frontiers in Endocrinology (Lausanne)","article-title":"Plasma metabolome profiling for the diagnosis of catecholamine producing tumors","volume":"12","author":"Marz","year":"2021","unstructured":"Marz JKurlbaum MRoche-Lancaster ODeutschbein TPeitzsch MPrehn CWeismann DRobledo MAdamski JFassnacht M, 2021Plasma metabolome profiling for the diagnosis of catecholamine producing tumors. Frontiers in Endocrinology (Lausanne)12 722656. (https:\/\/doi.org\/10.3389\/fendo.2021.722656)"},{"key":"bib66","series-title":"Endocrine Pathology","first-page":"90","article-title":"Overview of the 2022 WHO classification of paragangliomas and pheochromocytomas","volume":"33","author":"Mete","year":"2022","unstructured":"Mete OAsa SLGill AJKimura NDe Krijger RR & Tischler A2022Overview of the 2022 WHO classification of paragangliomas and pheochromocytomas. Endocrine Pathology3390\u2013114. (https:\/\/doi.org\/10.1007\/s12022-022-09704-6)"},{"key":"bib67","series-title":"Endocrine-Related Cancer","first-page":"375","article-title":"Preclinical evaluation of targeted therapies in Sdhb-mutated tumors","volume":"29","author":"Moog","year":"2022","unstructured":"Moog SSalgues BBraik-Djellas YViel TBalvay DAutret GRobidel EGimenez-Roqueplo APTavitian BLussey-Lepoutre C, 2022Preclinical evaluation of targeted therapies in Sdhb-mutated tumors. Endocrine-Related Cancer29375\u2013388. (https:\/\/doi.org\/10.1530\/ERC-22-0030)"},{"key":"bib68","series-title":"Cell Reports","first-page":"4551","article-title":"TET-mediated hypermethylation primes SDH-deficient cells for HIF2alpha-driven mesenchymal transition","volume":"30","author":"Morin","year":"2020","unstructured":"Morin AGoncalves JMoog SCastro-Vega LJJob SBuffet AFontenille MJWoszczyk JGimenez-Roqueplo APLetouze E, 2020TET-mediated hypermethylation primes SDH-deficient cells for HIF2alpha-driven mesenchymal transition. Cell Reports304551\u20134566.e7. (https:\/\/doi.org\/10.1016\/j.celrep.2020.03.022)"},{"key":"bib69","series-title":"European Journal of Endocrinology","first-page":"179","article-title":"Mass spectrometry imaging identifies metabolic patterns associated with malignant potential in pheochromocytoma and paraganglioma","volume":"185","author":"Murakami","year":"2021","unstructured":"Murakami MSun NGreunke CFeuchtinger AKircher SDeutschbein TPapathomas TBechmann NWilliam Wallace PPeitzsch M, 2021Mass spectrometry imaging identifies metabolic patterns associated with malignant potential in pheochromocytoma and paraganglioma. European Journal of Endocrinology185179\u2013191. (https:\/\/doi.org\/10.1530\/EJE-20-1407)"},{"key":"bib70","series-title":"Cardiovascular Diabetology","article-title":"Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults","volume":"20","author":"Osuna-Prieto","year":"2021","unstructured":"Osuna-Prieto FJMartinez-Tellez BOrtiz-Alvarez LDi XJurado-Fasoli LXu HCeperuelo-Mallafre VNunez-Roa CKohler ISegura-Carretero A, 2021Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults. Cardiovascular Diabetology20 151. (https:\/\/doi.org\/10.1186\/s12933-021-01333-3)"},{"key":"bib71","series-title":"European Journal of Cancer","first-page":"32","article-title":"Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma","volume":"169","author":"Pamporaki","year":"2022","unstructured":"Pamporaki CProdanov TMeuter LBerends AMABechmann NConstantinescu GBeuschlein FRemde HJanuszewicz AKerstens MN, 2022Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma. European Journal of Cancer16932\u201341. (https:\/\/doi.org\/10.1016\/j.ejca.2022.03.032)"},{"key":"bib72","series-title":"Molecular and Cellular Biology","first-page":"912","article-title":"Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro","volume":"27","author":"Pan","year":"2007","unstructured":"Pan YMansfield KDBertozzi CCRudenko VChan DAGiaccia AJ & Simon MC2007Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Molecular and Cellular Biology27912\u2013925. (https:\/\/doi.org\/10.1128\/MCB.01223-06)"},{"key":"bib74","series-title":"Clinical Cancer Research","first-page":"3423","article-title":"Targeting NAD(+)\/PARP DNA repair pathway as a novel therapeutic approach to SDHB-mutated cluster I pheochromocytoma and paraganglioma","volume":"24","author":"Pang","year":"2018","unstructured":"Pang YLu YCaisova VLiu YBullova PHuynh TTZhou YYu DFrysak ZHartmann I, 2018Targeting NAD(+)\/PARP DNA repair pathway as a novel therapeutic approach to SDHB-mutated cluster I pheochromocytoma and paraganglioma. Clinical Cancer Research243423\u20133432. (https:\/\/doi.org\/10.1158\/1078-0432.CCR-17-3406)"},{"key":"bib73","series-title":"Cancers (Basel)","article-title":"Pheochromocytomas and paragangliomas: from genetic diversity to targeted therapies","volume":"11","author":"Pang","year":"2019","unstructured":"Pang YLiu YPacak K & Yang C2019Pheochromocytomas and paragangliomas: from genetic diversity to targeted therapies. Cancers (Basel)11436. (https:\/\/doi.org\/10.3390\/cancers11040436)"},{"key":"bib75","series-title":"Clinical Chemistry","first-page":"1098","article-title":"Harmonization of LC-MS\/MS measurements of plasma free normetanephrine, metanephrine, and 3-methoxytyramine","volume":"67","author":"Peitzsch","year":"2021","unstructured":"Peitzsch MNovos TKaden DKurlbaum MVan Herwaarden AEMuller DAdaway JGrouzmann EMcwhinney BHoad K, 2021Harmonization of LC-MS\/MS measurements of plasma free normetanephrine, metanephrine, and 3-methoxytyramine. Clinical Chemistry671098\u20131112. (https:\/\/doi.org\/10.1093\/clinchem\/hvab060)"},{"key":"bib76","series-title":"Endocrine-Related Cancer","first-page":"533","article-title":"SDHx mutations and temozolomide in malignant pheochromocytoma and paraganglioma","volume":"29","author":"Perez","year":"2022","unstructured":"Perez KJacene HHornick JLMa CVaz NBrais LKAlexander HBaddoo WAstone KEsplin ED, 2022SDHx mutations and temozolomide in malignant pheochromocytoma and paraganglioma. Endocrine-Related Cancer29533\u2013544. (https:\/\/doi.org\/10.1530\/ERC-21-0392)"},{"key":"bib77","series-title":"Human Molecular Genetics","first-page":"2231","article-title":"Accumulation of Krebs cycle intermediates and over-expression of HIF1 alpha in tumours which result from germline FH and SDH mutations","volume":"14","author":"Pollard","year":"2005","unstructured":"Pollard PJBriere JJAlam NABarwell JBarclay EWortham NCHunt TMitchell MOlpin SMoat SJ, 2005Accumulation of Krebs cycle intermediates and over-expression of HIF1 alpha in tumours which result from germline FH and SDH mutations. Human Molecular Genetics142231\u20132239. (https:\/\/doi.org\/10.1093\/hmg\/ddi227)"},{"key":"bib78","series-title":"Journal of Hypertension","first-page":"2049","article-title":"Cardiovascular manifestations of phaeochromocytoma","volume":"29","author":"Prejbisz","year":"2011","unstructured":"Prejbisz ALenders JWEisenhofer G & Januszewicz A2011Cardiovascular manifestations of phaeochromocytoma. Journal of Hypertension292049\u20132060. (https:\/\/doi.org\/10.1097\/HJH.0b013e32834a4ce9)"},{"key":"bib79","series-title":"Journal of Nuclear Medicine","first-page":"623","article-title":"Efficacy and safety of high-specific-activity (131)I-MIBG therapy in patients with advanced pheochromocytoma or paraganglioma","volume":"60","author":"Pryma","year":"2019","unstructured":"Pryma DAChin BBNoto RBDillon JSPerkins SSolnes LKostakoglu LSerafini ANPampaloni MHJensen J, 2019Efficacy and safety of high-specific-activity (131)I-MIBG therapy in patients with advanced pheochromocytoma or paraganglioma. Journal of Nuclear Medicine60623\u2013630. (https:\/\/doi.org\/10.2967\/jnumed.118.217463)"},{"key":"bib80","series-title":"Metabolism: Clinical and Experimental","article-title":"Targeting pheochromocytoma\/paraganglioma with polyamine inhibitors","volume":"110","author":"Rai","year":"2020","unstructured":"Rai SKBril FHatch HMXu YShelton LKalavalapalli SClick ALee DBeecher CKirby A, 2020Targeting pheochromocytoma\/paraganglioma with polyamine inhibitors. Metabolism: Clinical and Experimental110 154297. (https:\/\/doi.org\/10.1016\/j.metabol.2020.154297)"},{"key":"bib81","series-title":"Clinical Cancer Research","first-page":"3787","article-title":"Genotype-specific abnormalities in mitochondrial function associate with distinct profiles of energy metabolism and catecholamine content in pheochromocytoma and paraganglioma","volume":"19","author":"Rao","year":"2013","unstructured":"Rao JUEngelke UFRodenburg RJWevers RAPacak KEisenhofer GQin NKusters BGoudswaard AGLenders JW, 2013Genotype-specific abnormalities in mitochondrial function associate with distinct profiles of energy metabolism and catecholamine content in pheochromocytoma and paraganglioma. Clinical Cancer Research193787\u20133795. (https:\/\/doi.org\/10.1158\/1078-0432.CCR-12-3922)"},{"key":"bib82","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"E214","article-title":"Genotype-specific differences in the tumor metabolite profile of pheochromocytoma and paraganglioma using untargeted and targeted metabolomics","volume":"100","author":"Rao","year":"2015","unstructured":"Rao JUEngelke UFSweep FCPacak KKusters BGoudswaard AGHermus ARMensenkamp AREisenhofer GQin N, 2015Genotype-specific differences in the tumor metabolite profile of pheochromocytoma and paraganglioma using untargeted and targeted metabolomics. Journal of Clinical Endocrinology and Metabolism100E214\u2013E222. (https:\/\/doi.org\/10.1210\/jc.2014-2138)"},{"key":"bib83","series-title":"Clinical Cancer Research","first-page":"6315","article-title":"Targeted exome sequencing of Krebs cycle genes reveals candidate cancer-predisposing mutations in pheochromocytomas and paragangliomas","volume":"23","author":"Remacha","year":"2017","unstructured":"Remacha LComino-Mendez IRichter SContreras LCurras-Freixes MPita GLeton RGalarreta ATorres-Perez RHonrado E, 2017Targeted exome sequencing of Krebs cycle genes reveals candidate cancer-predisposing mutations in pheochromocytomas and paragangliomas. Clinical Cancer Research236315\u20136324. (https:\/\/doi.org\/10.1158\/1078-0432.CCR-16-2250)"},{"key":"bib84","series-title":"Molecular Pharmacology","first-page":"240","article-title":"Structural basis for the allosteric inhibition of hypoxia-inducible factor (HIF)-2 by belzutifan","volume":"102","author":"Ren","year":"2022","unstructured":"Ren XDiao XZhuang J & Wu D2022Structural basis for the allosteric inhibition of hypoxia-inducible factor (HIF)-2 by belzutifan. Molecular Pharmacology102240\u2013247. (https:\/\/doi.org\/10.1124\/molpharm.122.000525)"},{"key":"bib85","series-title":"Genetics in Medicine","first-page":"405","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","unstructured":"Richards SAziz NBale SBick DDas SGastier-Foster JGrody WWHegde MLyon ESpector E, 2015Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine17405\u2013424. (https:\/\/doi.org\/10.1038\/gim.2015.30)"},{"key":"bib89","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"3903","article-title":"Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas\/paragangliomas due to succinate dehydrogenase deficiency","volume":"99","author":"Richter","year":"2014","unstructured":"Richter SPeitzsch MRapizzi ELenders JWQin NDe Cubas AASchiavi FRao JUBeuschlein FQuinkler M, 2014Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas\/paragangliomas due to succinate dehydrogenase deficiency. Journal of Clinical Endocrinology and Metabolism993903\u20133911. (https:\/\/doi.org\/10.1210\/jc.2014-2151)"},{"key":"bib86","series-title":"Cell and Tissue Research","first-page":"473","article-title":"Primary fibroblast co-culture stimulates growth and metabolism in Sdhb-impaired mouse pheochromocytoma MTT cells","volume":"374","author":"Richter","year":"2018","unstructured":"Richter SD'antongiovanni VMartinelli SBechmann NRiverso MPoitz DMPacak KEisenhofer GMannelli M & Rapizzi E2018Primary fibroblast co-culture stimulates growth and metabolism in Sdhb-impaired mouse pheochromocytoma MTT cells. Cell and Tissue Research374473\u2013485. (https:\/\/doi.org\/10.1007\/s00441-018-2907-x)"},{"key":"bib87","series-title":"Genetics in Medicine","first-page":"705","article-title":"Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma","volume":"21","author":"Richter","year":"2019","unstructured":"Richter SGieldon LPang YPeitzsch MHuynh TLeton RViana BErcolino TMangelis ARapizzi E, 2019Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma. Genetics in Medicine21705\u2013717. (https:\/\/doi.org\/10.1038\/s41436-018-0106-5)"},{"key":"bib88","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"359","article-title":"Epigenetic mutation of the succinate dehydrogenase C promoter in a patient with two paragangliomas","volume":"101","author":"Richter","year":"2016","unstructured":"Richter SKlink BNacke BDe Cubas AAMangelis ARapizzi EMeinhardt MSkondra CMannelli MRobledo M, 2016Epigenetic mutation of the succinate dehydrogenase C promoter in a patient with two paragangliomas. Journal of Clinical Endocrinology and Metabolism101359\u2013363. (https:\/\/doi.org\/10.1210\/jc.2015-3856)"},{"key":"bib90","series-title":"Endocrine-Related Cancer","first-page":"213","article-title":"Head\/neck paragangliomas: focus on tumor location, mutational status and plasma methoxytyramine","volume":"29","author":"Richter","year":"2022","unstructured":"Richter SQiu BGhering MKunath CConstantinescu GLuths CPamporaki CBechmann NMeuter LKwapiszewska A, 2022Head\/neck paragangliomas: focus on tumor location, mutational status and plasma methoxytyramine. Endocrine-Related Cancer29213\u2013224. (https:\/\/doi.org\/10.1530\/ERC-21-0359)"},{"key":"bib91","series-title":"European Journal of Endocrinology","first-page":"757","article-title":"Life-threatening events in patients with pheochromocytoma","volume":"173","author":"Riester","year":"2015","unstructured":"Riester AWeismann DQuinkler MLichtenauer UDSommerey SHalbritter RPenning RSpitzweg CSchopohl JBeuschlein F, 2015Life-threatening events in patients with pheochromocytoma. European Journal of Endocrinology173757\u2013764. (https:\/\/doi.org\/10.1530\/EJE-15-0483)"},{"key":"bib92","series-title":"Cancers (Basel)","article-title":"Glutaminases as a novel target for SDHB-associated pheochromocytomas\/paragangliomas","volume":"12","author":"Sarkadi","year":"2020","unstructured":"Sarkadi BMeszaros KKrencz ICanu LKrokker LZakarias SBarna GSebestyen APapay JHujber Z, 2020Glutaminases as a novel target for SDHB-associated pheochromocytomas\/paragangliomas. Cancers (Basel)12599. (https:\/\/doi.org\/10.3390\/cancers12030599)"},{"key":"bib93","series-title":"ISME Journal","first-page":"1642","article-title":"Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota","volume":"12","author":"Serena","year":"2018","unstructured":"Serena CCeperuelo-Mallafre VKeiran NQueipo-Ortuno MIBernal RGomez-Huelgas RUrpi-Sarda MSabater MPerez-Brocal VAndres-Lacueva C, 2018Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota. ISME Journal121642\u20131657. (https:\/\/doi.org\/10.1038\/s41396-018-0068-2)"},{"key":"bib94","series-title":"iScience","first-page":"63","article-title":"Chromatin succinylation correlates with active gene expression and is perturbed by defective TCA cycle metabolism","volume":"2","author":"Smestad","year":"2018","unstructured":"Smestad JErber LChen Y & Maher LJ2018Chromatin succinylation correlates with active gene expression and is perturbed by defective TCA cycle metabolism. iScience263\u201375. (https:\/\/doi.org\/10.1016\/j.isci.2018.03.012)"},{"key":"bib95","series-title":"Investigational New Drugs","first-page":"29","article-title":"Phase 1 study of N1-N11-diethylnorspermine (DENSPM) administered TID for 6 days in patients with advanced malignancies","volume":"19","author":"Streiff","year":"2001","unstructured":"Streiff RR & Bender JF2001Phase 1 study of N1-N11-diethylnorspermine (DENSPM) administered TID for 6 days in patients with advanced malignancies. Investigational New Drugs1929\u201339. (https:\/\/doi.org\/10.1023\/a:1006448516938)"},{"key":"bib96","series-title":"Nature Genetics","first-page":"1086","article-title":"Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair","volume":"50","author":"Sulkowski","year":"2018","unstructured":"Sulkowski PLSundaram RKOeck SCorso CDLiu YNoorbakhsh SNiger MBoeke MUeno DKalathil AN2018. Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair. Nature Genetics501086\u20131092. (https:\/\/doi.org\/10.1038\/s41588-018-0170-4)"},{"key":"bib97","series-title":"Nature Genetics","first-page":"406","article-title":"Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer","volume":"30","author":"Tomlinson","year":"2002","unstructured":"Tomlinson IPAlam NARowan AJBarclay EJaeger EEKelsell DLeigh IGorman PLamlum HRahman S, 2002Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nature Genetics30406\u2013410. (https:\/\/doi.org\/10.1038\/ng849)"},{"key":"bib98","series-title":"Theranostics","first-page":"278","article-title":"Epigenetic drugs in somatostatin type 2 receptor radionuclide theranostics and radiation transcriptomics in mouse pheochromocytoma models","volume":"13","author":"Ullrich","year":"2023","unstructured":"Ullrich MRichter SLiers JDrukewitz SFriedemann MKotzerke JZiegler CGNolting SKopka K & Pietzsch J2023Epigenetic drugs in somatostatin type 2 receptor radionuclide theranostics and radiation transcriptomics in mouse pheochromocytoma models. Theranostics13278\u2013294. (https:\/\/doi.org\/10.7150\/thno.77918)"},{"key":"bib99","series-title":"Analytical Chemistry","first-page":"9072","article-title":"In matrix derivatization combined with LC-MS\/MS results in ultrasensitive quantification of plasma free metanephrines and catecholamines","volume":"92","author":"van Faassen","year":"2020","unstructured":"van Faassen MBischoff REijkelenkamp KDe Jong WHAVan Der Ley CP & Kema IP2020In matrix derivatization combined with LC-MS\/MS results in ultrasensitive quantification of plasma free metanephrines and catecholamines. Analytical Chemistry929072\u20139078. (https:\/\/doi.org\/10.1021\/acs.analchem.0c01263)"},{"key":"bib100","series-title":"American Journal of Human Genetics","first-page":"153","article-title":"Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma","volume":"74","author":"Vanharanta","year":"2004","unstructured":"Vanharanta SBuchta MMcwhinney SRVirta SKPeczkowska MMorrison CDLehtonen RJanuszewicz AJarvinen HJuhola M, 2004Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma. American Journal of Human Genetics74153\u2013159. (https:\/\/doi.org\/10.1086\/381054)"},{"key":"bib101","series-title":"Endocrine-Related Cancer","first-page":"M1","article-title":"Magnetic resonance spectroscopy of paragangliomas: new insights into in vivo metabolomics","volume":"22","author":"Varoquaux","year":"2015","unstructured":"Varoquaux ALe Fur YImperiale AReyre AMontava MFakhry NNamer IJMoulin GPacak KGuye M, 2015Magnetic resonance spectroscopy of paragangliomas: new insights into in vivo metabolomics. Endocrine-Related Cancer22M1\u2013M8. (https:\/\/doi.org\/10.1530\/ERC-15-0246)"},{"key":"bib102","series-title":"Cancers (Basel)","article-title":"Favorable outcome in patients with pheochromocytoma and paraganglioma treated with 177Lu-DOTATATE","volume":"11","author":"Vyakaranam","year":"2019","unstructured":"Vyakaranam ARCrona JNorlen OGranberg DGarske-Roman USandstrom MFross-Baron KThiis-Evensen EHellman P & Sundin A2019Favorable outcome in patients with pheochromocytoma and paraganglioma treated with 177Lu-DOTATATE. Cancers (Basel)11909. (https:\/\/doi.org\/10.3390\/cancers11070909)"},{"key":"bib103","series-title":"Journal of Pathology","first-page":"378","article-title":"Metabolomics, machine learning and immunohistochemistry to predict succinate dehydrogenase mutational status in phaeochromocytomas and paragangliomas","volume":"251","author":"Wallace","year":"2020","unstructured":"Wallace PWConrad CBruckmann SPang YCaleiras EMurakami MKorpershoek EZhuang ZRapizzi EKroiss M, 2020Metabolomics, machine learning and immunohistochemistry to predict succinate dehydrogenase mutational status in phaeochromocytomas and paragangliomas. Journal of Pathology251378\u2013387. (https:\/\/doi.org\/10.1002\/path.5472)"},{"key":"bib104","series-title":"Metabolites","article-title":"Targeted quantification of carbon metabolites identifies metabolic progression markers and an undiagnosed case of SDH-deficient clear cell renal cell carcinoma in a German cohort","volume":"11","author":"William","year":"2021","unstructured":"William DErdmann KOttemoller JMangelis AConrad CPeitzsch MSchrock EEisenhofer GZacharis AFussel S, 2021Targeted quantification of carbon metabolites identifies metabolic progression markers and an undiagnosed case of SDH-deficient clear cell renal cell carcinoma in a German cohort. Metabolites11764. (https:\/\/doi.org\/10.3390\/metabo11110764)"},{"key":"bib105","series-title":"Analytical Chemistry","first-page":"708","article-title":"High resolution mass spectrometry","volume":"84","author":"Xian","year":"2012","unstructured":"Xian FHendrickson CL & Marshall AG2012High resolution mass spectrometry. Analytical Chemistry84708\u2013719. (https:\/\/doi.org\/10.1021\/ac203191t)"},{"key":"bib106","series-title":"Genes and Development","first-page":"1326","article-title":"Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors","volume":"26","author":"Xiao","year":"2012","unstructured":"Xiao MYang HXu WMa SLin HZhu HLiu LLiu YYang CXu Y, 2012Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes and Development261326\u20131338. (https:\/\/doi.org\/10.1101\/gad.191056.112)"},{"key":"bib107","series-title":"Cancer Cell","first-page":"709","article-title":"Succinate: a new epigenetic hacker","volume":"23","author":"Yang","year":"2013","unstructured":"Yang M & Pollard PJ2013Succinate: a new epigenetic hacker. Cancer Cell23709\u2013711. (https:\/\/doi.org\/10.1016\/j.ccr.2013.05.015)"},{"key":"bib108","series-title":"Metabolites","first-page":"640","article-title":"The Succinated proteome of FH-mutant tumours","volume":"4","author":"Yang","year":"2014","unstructured":"Yang MTernette NSu HDabiri RKessler BMAdam JTeh BT & Pollard PJ2014The Succinated proteome of FH-mutant tumours. Metabolites4640\u2013654. (https:\/\/doi.org\/10.3390\/metabo4030640)"},{"key":"bib109","series-title":"European Urology Focus","first-page":"1278","article-title":"Genomic and metabolic hallmarks of SDH- and FH-deficient renal cell carcinomas","volume":"8","author":"Yoo","year":"2022","unstructured":"Yoo ATang CZucker MFitzgerald KDinatale RGRappold PMWeiss KFreeman BLee CHSchultz N, 2022Genomic and metabolic hallmarks of SDH- and FH-deficient renal cell carcinomas. European Urology Focus81278\u20131288. (https:\/\/doi.org\/10.1016\/j.euf.2021.12.002)"},{"key":"bib110","series-title":"Cancer and Metabolism","article-title":"Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells","volume":"1","author":"Zheng","year":"2013","unstructured":"Zheng LMackenzie EDKarim SAHedley ABlyth KKalna GWatson DGSzlosarek PFrezza C & Gottlieb E2013Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells. Cancer and Metabolism1 12. (https:\/\/doi.org\/10.1186\/2049-3002-1-12)"},{"key":"bib111","series-title":"Journal of Clinical Investigation","first-page":"1167","article-title":"Role of AMP-activated protein kinase in mechanism of metformin action","volume":"108","author":"Zhou","year":"2001","unstructured":"Zhou GMyers RLi YChen YShen XFenyk-Melody JWu MVentre JDoebber TFujii N, 2001Role of AMP-activated protein kinase in mechanism of metformin action. Journal of Clinical Investigation1081167\u20131174. (https:\/\/doi.org\/10.1172\/JCI13505)"},{"key":"bib112","series-title":"Endocrinology and Metabolism Clinics of North America","first-page":"295","article-title":"Hypertension in pheochromocytoma: characteristics and treatment","volume":"40","author":"Zuber","year":"2011","unstructured":"Zuber SMKantorovich V & Pacak K2011Hypertension in pheochromocytoma: characteristics and treatment. Endocrinology and Metabolism Clinics of North America40295\u2013311, vii. 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