N Engl J Med. 2008 Dec 18;359(25):2685-92. doi: 10.1056/NEJMoa0806277.

PHD2 mutation and congenital erythrocytosis with paraganglioma.

Ladroue C, Carcenac R, Leporrier M, Gad S, Le Hello C, Galateau-Salle F, Feunteun J, Pouysségur J, Richard S, Gardie B.

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Génétique Oncologique, Ecole Pratique des Hautes Etudes and Centre National de la Recherche Scientifique (FRE 2939), Institut de Cancérologie Gustave Roussy, Villejuif, France.

Abstract

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.

2008 Massachusetts Medical Society

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PHD2 mutation and congenital erythrocytosis with paraganglioma. [N Engl J Med. 2009]
PHD2 mutation and congenital erythrocytosis with paraganglioma.Eltzschig HK, Eckle T, Grenz A. N Engl J Med. 2009 Mar 26; 360(13):1361-2; author reply 1362.

PMID:: 19092153; [PubMed - indexed for MEDLINE]

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PHD2 mutation and congenital erythrocytosis with paraganglioma. [N Engl J Med. 2009]
PHD2 mutation and congenital erythrocytosis with paraganglioma.
Eltzschig HK, Eckle T, Grenz A. N Engl J Med. 2009 Mar 26; 360(13):1361-2; author reply 1362.
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PHD2 mutation and congenital erythrocytosis with paraganglioma.
PHD2 mutation and congenital erythrocytosis with paraganglioma.
N Engl J Med. 2008 Dec 18 ;359(25):2685-92. doi: 10.1056/NEJMoa0806277.

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