{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSDHB is a nuclear‐encoded subunit of mitochondrial complex II that functions as a bona fide tumor suppressor. Germline inactivating mutations in SDHB have been shown to predispose carriers to a spectrum of neoplasias including pheochromocytomas, paragangliomas, renal cell carcinomas, and gastrointestinal stromal tumors, thereby defining distinct hereditary cancer syndromes. These genetic alterations have provided crucial insights into familial tumor predisposition and assist in guiding screening and clinical management strategies in affected families."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the biochemical level, SDHB operates as a vital component of complex II (succinate dehydrogenase), bridging the Krebs cycle and the electron transport chain. Loss‐of‐function mutations in SDHB result in the accumulation of succinate that competitively inhibits α–ketoglutarate–dependent dioxygenases, leading to widespread alterations in histone and DNA methylation. These perturbations promote a pseudohypoxic cellular state characterized by HIF stabilization and increased reactive oxygen species, events that drive metabolic reprogramming from oxidative phosphorylation toward glycolysis and enhance cell adhesion properties, thereby contributing to tumor initiation and progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, the functional status of SDHB has significant diagnostic and therapeutic implications. Immunohistochemical detection of SDHB protein is routinely used to identify tumors with SDH deficiency—such as pheochromocytomas, paragangliomas, gastrointestinal stromal tumors and certain renal neoplasms—with loss of SDHB staining correlating with increased malignancy risk and early metastatic behavior. This diagnostic tool not only streamlines genetic testing and family counseling but also informs treatment decisions; for instance, SDHB‐mutated tumors have shown distinct responses to targeted therapies such as temozolomide. In addition, systematic screening and refined imaging strategies, including cases with false‐negative MIBG uptake, further underscore the central role of SDHB alterations in personalized patient management."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "44"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hartmut P H Neumann, Birke Bausch, Sarah R McWhinney, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A role for mitochondrial enzymes in inherited neoplasia and beyond."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Cancer (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrc1013"}], "href": "https://doi.org/10.1038/nrc1013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12612654"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12612654"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sakari Vanharanta, Mary Buchta, Sarah R McWhinney, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21136"}], "href": "https://doi.org/10.1002/humu.21136"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19802898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19802898"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Christopher Ricketts, Emma R Woodward, Pip Killick, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2006-0423"}], "href": "https://doi.org/10.1210/jc.2006-0423"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16912137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16912137"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Henri J L M Timmers, Anna Kozupa, Graeme Eisenhofer, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Genetics of pheochromocytoma and paraganglioma in Spanish patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2008-2756"}], "href": "https://doi.org/10.1210/jc.2008-2756"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19258401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19258401"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "José Gaal, Nelly Burnichon, Esther Korpershoek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2009-2170"}], "href": "https://doi.org/10.1210/jc.2009-2170"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19915015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19915015"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Attje S Hoekstra, Jean-Pierre Bayley "}, {"type": "b", "children": [{"type": "t", "text": "The role of complex II in disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbabio.2012.11.005"}], "href": "https://doi.org/10.1016/j.bbabio.2012.11.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23174333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23174333"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Diana E Benn, Michael S Croxson, Kathy Tucker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1206300"}], "href": "https://doi.org/10.1038/sj.onc.1206300"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12618761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12618761"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Carsten Christof Boedeker, Hartmut P H Neumann, Wolfgang Maier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Malignant head and neck paragangliomas in SDHB mutation carriers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Otolaryngol Head Neck Surg (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.otohns.2007.01.015"}], "href": "https://doi.org/10.1016/j.otohns.2007.01.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17599579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17599579"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jean-Pierre Bayley, Ivonne van Minderhout, Marjan M Weiss, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2350-7-1"}], "href": "https://doi.org/10.1186/1471-2350-7-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16405730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16405730"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Mengtao Xiao, Hui Yang, Wei Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.191056.112"}], "href": "https://doi.org/10.1101/gad.191056.112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22677546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22677546"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Robert D Guzy, Bhumika Sharma, Eric Bell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01338-07"}], "href": "https://doi.org/10.1128/MCB.01338-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17967865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17967865"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Ana M Cervera, Jean-Pierre Bayley, Peter Devilee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of succinate dehydrogenase dysregulates histone modification in mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-8-89"}], "href": "https://doi.org/10.1186/1476-4598-8-89"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19849834"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19849834"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Neetu Saxena, Nunziata Maio, Daniel R Crooks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SDHB-Deficient Cancers: The Role of Mutations That Impair Iron Sulfur Cluster Delivery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Natl Cancer Inst (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jnci/djv287"}], "href": "https://doi.org/10.1093/jnci/djv287"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26719882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26719882"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Nunziata Maio, Daniele Ghezzi, Daniela Verrigni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disease-Causing SDHAF1 Mutations Impair Transfer of Fe-S Clusters to SDHB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2015.12.005"}], "href": "https://doi.org/10.1016/j.cmet.2015.12.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26749241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26749241"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Ana M Cervera, Nadezda Apostolova, Francisco Luna Crespo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cells silenced for SDHB expression display characteristic features of the tumor phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-5580"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-5580"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18519664"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18519664"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Young-Sil Yoon, Hae-Ok Byun, Hyeseong Cho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Complex II defect via down-regulation of iron-sulfur subunit induces mitochondrial dysfunction and cell cycle delay in iron chelation-induced senescence-associated growth arrest."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308489200"}], "href": "https://doi.org/10.1074/jbc.M308489200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14512425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14512425"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Laurence Amar, Jérôme Bertherat, Eric Baudin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic testing in pheochromocytoma or functional paraganglioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2005.03.1484"}], "href": "https://doi.org/10.1200/JCO.2005.03.1484"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16314641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16314641"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Katherine A Janeway, Su Young Kim, Maya Lodish, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1009199108"}], "href": "https://doi.org/10.1073/pnas.1009199108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21173220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21173220"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Barbara Pasini, Sarah R McWhinney, Thalia Bei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.ejhg.5201904"}], "href": "https://doi.org/10.1038/sj.ejhg.5201904"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17667967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17667967"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Laurence Amar, Eric Baudin, Nelly Burnichon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2007-0709"}], "href": "https://doi.org/10.1210/jc.2007-0709"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17652212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17652212"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Sosipatros A Boikos, Alberto S Pappo, J Keith Killian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular Subtypes of KIT/PDGFRA Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Gastrointestinal Stromal Tumor Clinic."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA Oncol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jamaoncol.2016.0256"}], "href": "https://doi.org/10.1001/jamaoncol.2016.0256"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27011036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27011036"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Markku Miettinen, Zeng-Feng Wang, Maarit Sarlomo-Rikala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0b013e3182260752"}], "href": "https://doi.org/10.1097/PAS.0b013e3182260752"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21997692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21997692"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Noriko Kimura, Ryoichi Takayanagi, Nae Takizawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr Relat Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/ERC-13-0494"}], "href": "https://doi.org/10.1530/ERC-13-0494"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24521857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24521857"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Anthony J Gill, Diana E Benn, Angela Chou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humpath.2009.12.005"}], "href": "https://doi.org/10.1016/j.humpath.2009.12.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20236688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20236688"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Anthony J Gill, Angela Chou, Ricardo Vilain, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Renal tumors associated with germline SDHB mutation show distinctive morphology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0b013e318227e7f4"}], "href": "https://doi.org/10.1097/PAS.0b013e318227e7f4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21934479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21934479"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Kathryn S King, Tamara Prodanov, Vitaly Kantorovich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metastatic pheochromocytoma/paraganglioma related to primary tumor development in childhood or adolescence: significant link to SDHB mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2011.34.6353"}], "href": "https://doi.org/10.1200/JCO.2011.34.6353"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21969497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21969497"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Joanne Ngeow, Jessica Mester, Lisa A Rybicki, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Clinical predictors and algorithm for the genetic diagnosis of pheochromocytoma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-09-1237"}], "href": "https://doi.org/10.1158/1078-0432.CCR-09-1237"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19825962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19825962"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Leonie Theresia van Hulsteijn, Olaf M Dekkers, Frederik J Hes, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Epithelial to mesenchymal transition is activated in metastatic pheochromocytomas and paragangliomas caused by SDHB gene mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2011-3437"}], "href": "https://doi.org/10.1210/jc.2011-3437"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22492777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22492777"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Maria A Pantaleo, Annalisa Astolfi, Milena Urbini, et al. 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