Brief Report: PHD2 Mutation and Congenital Erythrocytosis with Paraganglioma

被引：258

作者：

Ladroue, Charline ^{[1
,3
,4
]}

Carcenac, Romain ^{[1
,3
,4
]}

Leporrier, Michel ^{[5
]}

Gad, Sophie ^{[1
,3
,4
]}

Le Hello, Claire ^{[6
]}

Galateau-Salle, Francoise ^{[7
]}

Feunteun, Jean ^{[3
,4
]}

Pouyssegur, Jacques ^{[8
]}

Richard, Stephane ^{[1
,2
,3
,4
,9
]}

Gardie, Betty ^{[1
,3
,4
]}

机构：

[1] Univ Paris 11, Fac Med Paris Sud, Genet Oncol EPHE, F-94276 Le Kremlin Bicetre, France

[2] CHU Bicetre, Serv Urol, Ctr Pilote Tumeurs Rares, Inst Natl Canc & Assistance Publ Hop Paris, F-94276 Le Kremlin Bicetre, France

[3] Inst Gustave Roussy, Ecole Prat Hautes Etud, Villejuif, France

[4] Inst Gustave Roussy, CNRS, FRE 2939, Villejuif, France

[5] CHU Caen, Serv Hematol Clin, F-14000 Caen, France

[6] CHU Caen, Serv Chirurg Thorac & Cardiovasc, F-14000 Caen, France

[7] CHU Caen, Lab Anat & Cytol Pathol, F-14000 Caen, France

[8] Univ Nice, Inst Dev Biol & Canc Res, CNRS, UMR 6543, Nice, France

[9] Hop Necker Enfants Malad, Serv Nephrol, Paris, France

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2008年 / 359卷 / 25期

关键词：

D O I：

10.1056/NEJMoa0806277

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2685 / 2692

页数：8

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