ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2013
New syndrome of paraganglioma and somatostatinoma associated with polycythemia.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Guideline
- ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors.Neuroendocrinology · 2016Guideline
- Multi-omic analysis identifies a multi-step pathology in a case of multiple chorangioma syndrome in monochorionic twins.Orphanet journal of rare diseases · 2026Article
- Assessment of HIF2α mutational pathogenicity using microscale thermophoresis.Biology methods & protocols · 2026Review
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- Redefining chronic mountain sickness: insights from high-altitude research and clinical experience.Medical review (2021) · 2025Review
- Head and neck paraganglioma in Pacak-Zhuang syndrome.JNCI cancer spectrum · 2025Article
- Case report - Adrenal collision tumour composed of oncocytoma and pheochromocytoma.Frontiers in oncology · 2025Article
- Hypoxia Inducible Factor-2α (HIF-2α) Pathway Inhibitors.Journal of kidney cancer and VHL · 2025Review
- International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents.Nature reviews. Endocrinology · 2024Review
- [Review and prospect of the diagnosis and treatment of head and neck paragangliomas].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2024Review
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- Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma.Journal of the Endocrine Society · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Deficiency in PHD2-mediated hydroxylation of HIF2α underlies Pacak-Zhuang syndrome.Communications biology · 2024Article
- Congenital Cyanotic Heart Disease and the Association with Pheochromocytomas and Paragangliomas.Current cardiology reports · 2023Review
- Pacak-Zhuang syndrome: a model providing new insights into tumor syndromes.Endocrine-related cancer · 2023Review
- Cytoplasmic HIF-2α as tissue biomarker to identify metastatic sympathetic paraganglioma.Scientific reports · 2023Article
- Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe occurrence of ≥ two distinct types of tumors, one of them paraganglioma (PGL), is unusual in an individual patient, except in hereditary cancer syndromes. PATIENTS AND
methodsFour unrelated patients were investigated, with thorough clinical evaluation. Plasma and tissue catecholamines and metanephrines were measured by high-performance liquid chromatography. Anatomic and functional imaging were performed for tumor visualization. Germline and tumor tissue DNA were analyzed for hypoxia-inducible factor 2 alpha (HIF2A) mutations. The prolyl hydroxylation and stability of the mutant HIF2α protein, transcriptional activity of mutant HIF2A, and expression of hypoxia-related genes were also investigated. Immunohistochemical staining for HIF1/2α was performed on formalin-fixed, paraffin-embedded tumor tissue.
resultsPatients were found to have polycythemia, multiple PGLs, and duodenal somatostatinomas by imaging or biochemistry with somatic gain-of-function HIF2A mutations. Each patient carried an identical unique mutation in both types of tumors but not in germline DNA. The HIF2A mutations in these patients were clustered adjacent to an oxygen-sensing proline residue, affecting HIF2α interaction with the prolyl hydroxylase domain 2-containing protein, decreasing the hydroxylation of HIF2α, and reducing HIF2α affinity for the von Hippel-Lindau protein and its degradation. An increase in the half-life of HIF2α was associated with upregulation of the hypoxia-related genes EPO, VEGFA, GLUT1, and END1 in tumors.
conclusionOur findings indicate the existence of a new syndrome with multiple PGLs and somatostatinomas associated with polycythemia. This new syndrome results from somatic gain-of-function HIF2A mutations, which cause an upregulation of hypoxia-related genes, including EPO and genes important in cancer biology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.