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PHD2 Mutation and Congenital Erythrocytosis with Paraganglioma
Open accessAbstract
Prolyl hydroxylase domain (PHD) proteins play a major role in regulating the hypoxia-inducible factor (HIF) that induces expression of genes involved in angiogenesis, erythropoiesis, and cell metabolism, proliferation, and survival. Germ-line mutations in the prolyl hydroxylase domain 2 gene (PHD2) have been reported in patients with familial erythrocytosis but not in association with tumors. We describe a patient with erythrocytosis and recurrent paraganglioma who carries a newly discovered PHD2 mutation. This mutation affects PHD2 function and stabilizes HIF-alpha proteins. In addition, we demonstrate loss of heterozygosity of PHD2 in the tumor, suggesting that PHD2 could be a tumor-suppressor gene.
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“Furthermore, H374R was associated with paraganglioma development”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [161]
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“Patients, who were heterozygous for these mutations were characterized by increased rbc values in the presence of inappropriately normal serum EPO levels. 157–162”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [161]
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“indicating that PHD2 may functions as a tumor suppressor.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [161]
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Self-citation
Metadata
- Authors
- Ladroue, C., Carcenac, R., Leporrier, M., Gad, S., Le Hello, C., Galateau-Salle, F., Feunteun, J., Pouysségur, J., Richard, S., & Gardie, B.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-12-18
- Volume
- 359
- Issue
- 25
- Pages
- 2685-2692
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2169448152
- Cited by
- 323
- References
- 25
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 8 · 2023: 10 · 2022: 7 · 2021: 17 · 2020: 11 · 2019: 17 · 2018: 15 · 2017: 21 · 2016: 29 · 2015: 16 · 2014: 33 · 2013: 31 · 2012: 20
- FWCI
- 23.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- prolyl hydroxylase domain 2, congenital erythrocytosis, paraganglioma, hypoxia-inducible factor, loss of heterozygosity, tumor suppressor, germline mutations, familial erythrocytosis
- MeSH terms
- Hemochromatosis Protein, Adult, Female, Homozygote, Humans, Male, Mediastinal Neoplasms, Membrane Proteins, Paraganglioma, Pedigree, Polycythemia, Procollagen-Proline Dioxygenase, Histocompatibility Antigens Class I, Neoplasms, Second Primary, Sequence Analysis, DNA, Germ-Line Mutation, Loss of Heterozygosity, Hypoxia-Inducible Factor-Proline Dioxygenases
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