FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 359:2685-2692 December 18, 2008 Number 25 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

SUMMARY

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- proteins. In addition, we demonstrate loss of heterozygosity of PHD2 in the tumor, suggesting that PHD2 could be a tumor-suppressor gene.

Source Information

From Génétique Oncologique, Ecole Pratique des Hautes Etudes (EPHE) and Centre National de la Recherche Scientifique (CNRS) (FRE 2939), Institut de Cancérologie Gustave Roussy, Villejuif (C. Ladroue, R.C., S.G., J.F., S.R., B.G.); Faculté de Médecine Paris-Sud, Université Paris-Sud (C. Ladroue, R.C., S.G., S.R., B.G.), and Centre Pilote Tumeurs Rares, Institut National du Cancer and Assistance Publique–Hôpitaux de Paris, Service d'Urologie, Centre Hospitalier Universitaire de Bicêtre (S.R.) — both in Le Kremlin Bicêtre; Service d'Hématologie Clinique (M.L.), Service de Chirurgie Thoracique et Cardio-Vasculaire (C. Le Hello), and Laboratoire d'Anatomie et Cytologie Pathologiques (F.G.-S.), Centre Hospitalier Universitaire, Caen; Institute of Developmental Biology and Cancer Research, CNRS (UMR 6543) University of Nice, Nice (J.P.); and Service de Néphrologie, Hôpital Necker, Paris (S.R.) — all in France.

Ms. Ladroue and Mr. Carcenac contributed equally to this article.

Address reprint requests to Dr. Richard at Génétique Oncologique EPHE, Faculté de Médecine Paris-Sud, 63 Rue Gabriel Péri, 94276 Le Kremlin-Bicêtre, France, or at stephane.richard{at}u-psud.fr.

Full Text of this Article

Related Letters:

PHD2 Mutation and Congenital Erythrocytosis with Paraganglioma
Eltzschig H. K., Eckle T., Grenz A., Gardie B., Feunteun J., Richard S.
Extract | Full Text | PDF  
N Engl J Med 2009; 360:1361-1362, Mar 26, 2009. Correspondence

This article has been cited by other articles:

• Minamishima, Y. A., Moslehi, J., Padera, R. F., Bronson, R. T., Liao, R., Kaelin, W. G. Jr. (2009). A Feedback Loop Involving the Phd3 Prolyl Hydroxylase Tunes the Mammalian Hypoxic Response In Vivo. Mol. Cell. Biol. 29: 5729-5741 [Abstract] [Full Text]  
• Tennant, D. A., Duran, R. V., Boulahbel, H., Gottlieb, E. (2009). Metabolic transformation in cancer. Carcinogenesis 30: 1269-1280 [Abstract] [Full Text]  
• Grunfeld, J.-P. (2009). Lessons from Rare Renal and Adrenal Diseases. CJASN 4: 870-872 [Full Text]  
• Eltzschig, H. K., Eckle, T., Grenz, A., Gardie, B., Feunteun, J., Richard, S. (2009). PHD2 Mutation and Congenital Erythrocytosis with Paraganglioma. NEJM 360: 1361-1362 [Full Text]  
• (2008). Hypoxia-Inducible Factor, Erythrocytosis, and Tumor Development. JWatch Oncology and Hematology 2008: 1-1 [Full Text]