{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:23:53Z","timestamp":1792175033291,"version":"4.4.0"},"reference-count":96,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors that arise from chromaffin cells. PHEOs arise from the adrenal medulla, whereas PGLs arise from the neural crest localized outside the adrenal gland. Approximately 40% of all cases of PPGLs (pheochromocytomas\/paragangliomas) are associated with germline mutations and 30\u201340% display somatic driver mutations. The mutations associated with PPGLs can be classified into three groups. The pseudohypoxic group or cluster I includes the following genes: SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, VHL, IDH1\/2, MHD2, EGLN1\/2 and HIF2\/EPAS; the kinase group or cluster II includes RET, NF1, TMEM127, MAX and HRAS; and the Wnt signaling group or cluster III includes CSDE1 and MAML3. Underlying mutations can help understand the clinical presentation, overall prognosis and surveillance follow-up. Here we are discussing the new genetic insights of PPGLs.<\/jats:p>","DOI":"10.3390\/cancers14030594","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T20:44:33Z","timestamp":1643143473000},"page":"594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["New Insights on the Genetics of Pheochromocytoma and Paraganglioma and Its Clinical Implications"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5754-1233","authenticated-orcid":false,"given":"Sakshi","family":"Jhawar","sequence":"first","affiliation":[{"name":"Life Bridge Health Center, Internal Medicine Program, Sinai Hospital of Baltimore, Baltimore, MD 21215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Arakawa","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Varghese","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-9024","authenticated-orcid":false,"given":"Yoo Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6514-5468","authenticated-orcid":false,"given":"Nitin","family":"Roper","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fathi","family":"Elloumi","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Pommier","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Pacak","sequence":"additional","affiliation":[{"name":"Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-4030","authenticated-orcid":false,"given":"Jaydira","family":"Del Rivero","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"ref_1","first-page":"802","article-title":"Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979","volume":"58","author":"Beard","year":"1983","journal-title":"Mayo Clin. Proc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1097\/MPA.0b013e3181ebb4f0","article-title":"The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: Pheochromocytoma, paraganglioma, and medullary thyroid cancer","volume":"39","author":"Chen","year":"2010","journal-title":"Pancreas"},{"key":"ref_3","first-page":"354","article-title":"Prevalence of clinically unsuspected pheochromocytoma. Review of a 50-year autopsy series","volume":"56","author":"Sutton","year":"1981","journal-title":"Mayo Clin. Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jamcollsurg.2009.09.022","article-title":"Clinical Spectrum of Pheochromocytoma","volume":"209","author":"Guerrero","year":"2009","journal-title":"J. Am. Coll. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0140-6736(05)67139-5","article-title":"Phaeochromocytoma","volume":"366","author":"Lenders","year":"2005","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ccell.2017.01.001","article-title":"Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma","volume":"31","author":"Fishbein","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.trecan.2017.11.001","article-title":"Genomic Landscape of Pheochromocytoma and Paraganglioma","volume":"4","author":"Jochmanova","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3974","DOI":"10.1093\/hmg\/ddr324","article-title":"Integrative genomic analysis reveals somatic mutations in pheochromocytoma and paraganglioma","volume":"20","author":"Burnichon","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/gim.2014.147","article-title":"A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: Referral indications for cancer predisposition assessment","volume":"17","author":"Hampel","year":"2015","journal-title":"Genet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1210\/jc.2014-1498","article-title":"Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline","volume":"99","author":"Lenders","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrc3648","article-title":"Pheochromocytoma and paraganglioma pathogenesis: Learning from genetic heterogeneity","volume":"14","author":"Dahia","year":"2014","journal-title":"Nat. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrendo.2014.188","article-title":"Paraganglioma and phaeochromocytoma: From genetics to personalized medicine","volume":"11","author":"Favier","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1200\/JCO.2011.34.6353","article-title":"Metastatic Pheochromocytoma\/Paraganglioma Related to Primary Tumor Development in Childhood or Adolescence: Significant Link to SDHB Mutations","volume":"29","author":"King","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.urology.2014.01.007","article-title":"The Genetic Basis of Pheochromocytoma and Paraganglioma: Implications for Management","volume":"83","author":"Shuch","year":"2014","journal-title":"Urology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1159\/000499497","article-title":"Peptide Receptor Radionuclide Therapy as a Novel Treatment for Metastatic and Invasive Phaeochromocytoma and Paraganglioma","volume":"109","author":"Mak","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1210\/jc.2017-00816","article-title":"Efficacy of Peptide Receptor Radionuclide Therapy for Functional Metastatic Paraganglioma and Pheochromocytoma","volume":"102","author":"Kong","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13550-019-0484-y","article-title":"Concomitant 177Lu-DOTATATE and capecitabine therapy in malignant paragangliomas","volume":"9","author":"Yadav","year":"2019","journal-title":"EJNMMI Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1002\/cncr.23812","article-title":"Treatment of malignant pheochromocytoma\/paraganglioma with cyclophosphamide, vincristine, and dacarbazine","volume":"113","author":"Huang","year":"2008","journal-title":"Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11864-020-00787-z","article-title":"Emerging Treatments for Advanced\/Metastatic Pheochromocytoma and Paraganglioma","volume":"21","author":"Ilanchezhian","year":"2020","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s12022-013-9269-4","article-title":"Usefulness of Negative and Weak\u2013Diffuse Pattern of SDHB Immunostaining in Assessment of SDH Mutations in Paragangliomas and Pheochromocytomas","volume":"24","author":"Castelblanco","year":"2013","journal-title":"Endocr. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/s41574-021-00492-3","article-title":"International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers","volume":"17","author":"Amar","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4675","DOI":"10.1038\/sj.onc.1209594","article-title":"Succinate dehydrogenase and fumarate hydratase: Linking mitochondrial dysfunction and cancer","volume":"25","author":"King","year":"2006","journal-title":"Oncogene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1158\/1078-0432.CCR-15-1841","article-title":"Recurrent Mutations of Chromatin-Remodeling Genes and Kinase Receptors in Pheochromocytomas and Paragangliomas","volume":"22","author":"Toledo","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1158\/1078-0432.CCR-10-0420","article-title":"SDHAF2 (PGL2-SDH5) and Hereditary Head and Neck Paraganglioma","volume":"17","author":"Kunst","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1093\/hmg\/ddt639","article-title":"Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas","volume":"23","author":"Buffet","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E2046","DOI":"10.1210\/jc.2014-1659","article-title":"Germline FH Mutations Presenting With Pheochromocytoma","volume":"99","author":"Clark","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1038\/s41436-018-0068-7","article-title":"Role of MDH2 pathogenic variant in pheochromocytoma and paraganglioma patients","volume":"20","author":"Calsina","year":"2018","journal-title":"Genet. Med."},{"key":"ref_28","first-page":"djv053","article-title":"Whole-Exome Sequencing Identifies MDH2 as a New Familial Paraganglioma Gene","volume":"107","author":"Contreras","year":"2015","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00109-012-0967-z","article-title":"A novel EPAS1\/HIF2A germline mutation in a congenital polycythemia with paraganglioma","volume":"91","author":"Lorenzo","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1530\/ERC-16-0231","article-title":"Novel insights into the polycythemia\u2013paraganglioma\u2013somatostatinoma syndrome","volume":"23","author":"Nambuba","year":"2016","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1200\/JCO.2012.47.1912","article-title":"New Syndrome of Paraganglioma and Somatostatinoma Associated With Polycythemia","volume":"31","author":"Pacak","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_32","first-page":"93","article-title":"Germ-line PHD1 and PHD2 mutations detected in patients with pheochromocytoma\/paraganglioma-polycythemia","volume":"93","author":"Yang","year":"2015","journal-title":"Klin. Wochenschr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6140","DOI":"10.1038\/ncomms7140","article-title":"Whole-exome sequencing identifies somatic ATRX mutations in pheochromocytomas and paragangliomas","volume":"6","author":"Fishbein","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1210\/er.2017-00062","article-title":"New Perspectives on Pheochromocytoma and Paraganglioma: Toward a Molecular Classification","volume":"38","author":"Crona","year":"2017","journal-title":"Endocr. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nrg3173","article-title":"Histone methylation: A dynamic mark in health, disease and inheritance","volume":"13","author":"Greer","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.2106\/JBJS.CC.L.00155","article-title":"Multicentric Giant Cell Tumor of Bone and Paraganglioma: A Case Report","volume":"3","author":"Iwata","year":"2013","journal-title":"JBJS Case Connect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data: Figure 1","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2015.01.003","article-title":"miR-375 regulates the canonical Wnt pathway through FZD8 silencing in arthritis synovial fibroblasts","volume":"164","author":"Miao","year":"2015","journal-title":"Immunol. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1158\/0008-5472.CAN-17-2463","article-title":"Germline Mutations in the Mitochondrial 2-Oxoglutarate\/Malate Carrier SLC25A11 Gene Confer a Predisposition to Metastatic Paragangliomas","volume":"78","author":"Buffet","year":"2018","journal-title":"Cancer Res."},{"key":"ref_41","first-page":"289","article-title":"Antiporters of the Mitochondrial Carrier Family","volume":"73","author":"Palmieri","year":"2014","journal-title":"Chloride Channels"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Pang, Y., Gupta, G., Yang, C., Wang, H., Huynh, T.-T., Abdullaev, Z., Pack, S.D., Percy, M.J., Lappin, T.R.J., and Zhuang, Z. (2018). A novel splicing site IRP1 somatic mutation in a patient with pheochromocytoma and JAK2V617F positive polycythemia vera: A case report. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4127-x"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.ajhg.2019.04.010","article-title":"Recurrent Germline DLST Mutations in Individuals with Multiple Pheochromocytomas and Paragangliomas","volume":"104","author":"Remacha","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1093\/jnci\/djab158","article-title":"Germline SUCLG2 Variants in Patients With Pheochromocytoma and Paraganglioma","volume":"114","author":"Vanova","year":"2021","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1158\/1541-7786.MCR-20-0992","article-title":"Mastermind Like Transcriptional Coactivator 3 (MAML3) Drives Neuroendocrine Tumor Progression","volume":"19","author":"Alzofon","year":"2021","journal-title":"Mol. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nsmb1222","article-title":"Iron-regulatory proteins limit hypoxia-inducible factor-2\u03b1 expression in iron deficiency","volume":"14","author":"Sanchez","year":"2007","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1158\/1078-0432.CCR-17-3406","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","journal-title":"Clin. Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1016\/S0960-894X(03)00539-0","article-title":"2-Oxoglutarate analogue inhibitors of hif prolyl hydroxylase","volume":"13","author":"Mole","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101416","DOI":"10.1016\/j.beem.2020.101416","article-title":"An overview of 20 years of genetic studies in pheochromocytoma and paraganglioma","volume":"34","author":"Buffet","year":"2020","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nature05610","article-title":"Patterns of somatic mutation in human cancer genomes","volume":"446","author":"Greenman","year":"2007","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/ng0597-68","article-title":"Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas","volume":"16","author":"Schmidt","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"27580","DOI":"10.1074\/jbc.273.42.27580","article-title":"Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes","volume":"273","author":"Johnson","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ccr.2004.11.022","article-title":"Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-\u03b1 prolyl hydroxylase","volume":"7","author":"Selak","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbadis.2011.01.013","article-title":"The interplay between SUCLA2, SUCLG2, and mitochondrial DNA depletion","volume":"1812","author":"Miller","year":"2011","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1042\/BCJ20160594","article-title":"Two transgenic mouse models for beta-subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations","volume":"473","author":"Kacso","year":"2016","journal-title":"Biochem. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8812","DOI":"10.1200\/JCO.2005.03.1484","article-title":"Genetic Testing in Pheochromocytoma or Functional Paraganglioma","volume":"23","author":"Amar","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1136\/jmedgenet-2018-105714","article-title":"Targeted next-generation sequencing detects rare genetic events in pheochromocytoma and paraganglioma","volume":"56","author":"Pigny","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1136\/jmedgenet-2017-105127","article-title":"Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD","volume":"55","author":"Andrews","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_59","first-page":"1019","article-title":"Ouabain-insensitive K+ and Na+ fluxes in frog muscle","volume":"28","author":"Marikian","year":"1983","journal-title":"Biofizika"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1210\/jc.2005-1862","article-title":"Clinical Presentation and Penetrance of Pheochromocytoma\/Paraganglioma Syndromes","volume":"91","author":"Benn","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3822","DOI":"10.1210\/jc.2007-0709","article-title":"Succinate Dehydrogenase B Gene Mutations Predict Survival in Patients with Malignant Pheochromocytomas or Paragangliomas","volume":"92","author":"Amar","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1001\/jama.292.8.943","article-title":"Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations","volume":"292","author":"Neumann","year":"2004","journal-title":"JAMA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4710","DOI":"10.1210\/jc.2016-1665","article-title":"A SDHC Founder Mutation Causes Paragangliomas (PGLs) in the French Canadians: New Insights on the SDHC-Related PGL","volume":"101","author":"Bourdeau","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1136\/jmedgenet-2016-104297","article-title":"Risk assessment of maternally inherited SDHD paraganglioma and phaeochromocytoma","volume":"54","author":"Burnichon","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1056\/NEJMra1806651","article-title":"Pheochromocytoma and Paraganglioma","volume":"381","author":"Neumann","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1007\/s00432-020-03138-5","article-title":"Clinical characteristics and outcomes of SDHB-related pheochromocytoma and paraganglioma in children and adolescents","volume":"146","author":"Jochmanova","year":"2020","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1136\/jcp.46.8.734","article-title":"Biochemical detection of phaeochromocytoma: Should we still be measuring urinary HMMA?","volume":"46","author":"Peaston","year":"1993","journal-title":"J. Clin. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1093\/oxfordjournals.aje.a113947","article-title":"Biochemical screening for pheochromocytoma. Superiority of urinary metanephrines measurements","volume":"120","author":"Manu","year":"1984","journal-title":"Am. J. Epidemiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1148\/rg.2017170043","article-title":"Imaging of Nonmalignant Adrenal Lesions in Children","volume":"37","author":"Sargar","year":"2017","journal-title":"Radiographics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/s41431-018-0116-4","article-title":"Clinical progression and metachronous paragangliomas in a large cohort of SDHD germline variant carriers","volume":"26","author":"Heesterman","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.ecl.2019.05.006","article-title":"Pheochromocytoma and Pregnancy","volume":"48","author":"Lenders","year":"2019","journal-title":"Endocrinol. Metab. Clin."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00191","article-title":"Translating in vivo metabolomic analysis of succinate dehydrogenase deficient tumours into clinical utility","volume":"2","author":"Casey","year":"2018","journal-title":"JCO Precis. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/j.1365-2265.2008.03368.x","article-title":"SDHC mutation in an elderly patient without familial antecedents","volume":"69","author":"Kusak","year":"2008","journal-title":"Clin. Endocrinol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1254\/jjp.53.499","article-title":"Stimulation of Oxygen Consumption of Platelets by Solcoseryl and Cardiocrome during In Vitro Aging for 5 Days","volume":"53","author":"Shimizu","year":"1990","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"E710","DOI":"10.1210\/jc.2014-4297","article-title":"Pituitary Adenoma With Paraganglioma\/Pheochromocytoma (3PAs) and Succinate Dehydrogenase Defects in Humans and Mice","volume":"100","author":"Xekouki","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1210\/en.2019-00410","article-title":"Synergistic Highly Potent Targeted Drug Combinations in Different Pheochromocytoma Models Including Human Tumor Cultures","volume":"160","author":"Fankhauser","year":"2019","journal-title":"Endocrinology"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ghayee, H.K., Bhagwandin, V.J., Stastny, V., Click, A., Ding, L.-H., Mizrachi, D., Zou, Y., Chari, R., Lam, W.L., and Bachoo, R.M. (2013). Progenitor Cell Line (hPheo1) Derived from a Human Pheochromocytoma Tumor. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065624"},{"key":"ref_78","first-page":"267","article-title":"Application of pluripotent stem cells for treatment of human neuroendocrine disorders","volume":"375","author":"Suga","year":"2018","journal-title":"Z. Zellforsch. Mikrosk. Anat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e101654","DOI":"10.15252\/embj.2019101654","article-title":"Xenograft and organoid model systems in cancer research","volume":"38","author":"Bleijs","year":"2019","journal-title":"EMBO J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1530\/ERC-19-0474","article-title":"A xenograft and cell line model of SDH-deficient pheochromocytoma derived from Sdhb+\/\u2212 rats","volume":"27","author":"Powers","year":"2020","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrendo.2016.185","article-title":"Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas","volume":"13","author":"Toledo","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.critrevonc.2017.05.005","article-title":"Review of sequencing platforms and their applications in phaeochromocytoma and paragangliomas","volume":"116","author":"Pillai","year":"2017","journal-title":"Crit. Rev. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"14","DOI":"10.15586\/jkcvhl.2018.113","article-title":"Clinical Syndromes and Genetic Screening Strategies of Pheochromocytoma and Paraganglioma","volume":"5","author":"Liu","year":"2018","journal-title":"J. Kidney Cancer VHL"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ando.2019.04.003","article-title":"Emerging molecular markers of metastatic pheochromocytomas and paragangliomas","volume":"80","author":"Goncalves","year":"2019","journal-title":"Ann. d\u2019Endocrinol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1210\/clinem\/dgz168","article-title":"Transcriptome Analysis of lncRNAs in Pheochromocytomas and Paragangliomas","volume":"105","author":"Job","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4946","DOI":"10.7150\/thno.35458","article-title":"Integrative multi-omics analysis identifies a prognostic miRNA signature and a targetable miR-21-3p\/TSC2\/mTOR axis in metastatic pheochromocytoma\/paraganglioma","volume":"9","author":"Calsina","year":"2019","journal-title":"Theranostics"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1158\/1078-0432.CCR-14-2804","article-title":"DNA Methylation Profiling in Pheochromocytoma and Paraganglioma Reveals Diagnostic and Prognostic Markers","volume":"21","author":"Korpershoek","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"44943","DOI":"10.1038\/srep44943","article-title":"Global DNA Methylation Analysis Identifies Two Discrete clusters of Pheochromocytoma with Distinct Genomic and Genetic Alterations","volume":"7","author":"Backman","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/PAS.0b013e31823d07f3","article-title":"Somatostatin Receptor Subtype 2A Immunohistochemistry Using a New Monoclonal Antibody Selects Tumors Suitable for In Vivo Somatostatin Receptor Targeting","volume":"36","author":"Waser","year":"2012","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/PAS.0000000000001190","article-title":"Molecular Profiling of Pheochromocytoma and Abdominal Paraganglioma Stratified by the PASS Algorithm Reveals Chromogranin B as Associated With Histologic Prediction of Malignant Behavior","volume":"43","author":"Stenman","year":"2019","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"R128","DOI":"10.1093\/hmg\/ddaa201","article-title":"Genetic stratification of inherited and sporadic phaeochromocytoma and paraganglioma: Implications for precision medicine","volume":"29","author":"Casey","year":"2020","journal-title":"Hum. Mol. Genet"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1097\/HJH.0000000000002438","article-title":"Genetics, diagnosis, management and future directions of research of phaeochromocytoma and paraganglioma: A position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension","volume":"38","author":"Lenders","year":"2020","journal-title":"J. Hypertens."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"N\u00f6lting, S., Ullrich, M., Pietzsch, J., Ziegler, C.G., Eisenhofer, G., Grossman, A., and Pacak, K. (2019). Current Management of Pheochromocytoma\/Paraganglioma: A Guide for the Practicing Clinician in the Era of Precision Medicine. Cancers, 11.","DOI":"10.3390\/cancers11101505"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1055\/a-0715-1888","article-title":"Metastatic Phaeochromocytoma: Spinning Towards More Promising Treatment Options","volume":"127","author":"Grossman","year":"2019","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Tabebi, M., Dutta, R.K., Skoglund, C., S\u00f6derkvist, P., and Gimm, O. (2022). Loss of SDHB Induces a Metabolic Switch in the hPheo1 Cell Line toward Enhanced OXPHOS. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010560"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/path.5472","article-title":"Metabolomics, machine learning and immunohistochemistry to predict succinate dehydrogenase mutational status in phaeochromocytomas and paragangliomas","volume":"251","author":"Wallace","year":"2020","journal-title":"J. Pathol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/3\/594\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:07:08Z","timestamp":1760134028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/3\/594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,25]]},"references-count":96,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cancers14030594"],"URL":"https:\/\/doi.org\/10.3390\/cancers14030594","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,25]]}}}