title: PHD2 mutation and congenital erythrocytosis with paraganglioma.
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.
authors.affiliation: Génétique Oncologique, Ecole Pratique des Hautes Etudes and Centre National de la Recherche Scientifique (FRE 2939), Institut de Cancérologie Gustave Roussy, Villejuif, France.
authors.forename: Charline
authors.initials: C
authors.lastname: Ladroue
authors.forename: Romain
authors.initials: R
authors.lastname: Carcenac
authors.forename: Michel
authors.initials: M
authors.lastname: Leporrier
authors.forename: Sophie
authors.initials: S
authors.lastname: Gad
authors.forename: Claire
authors.initials: C
authors.lastname: Le Hello
authors.forename: Françoise
authors.initials: F
authors.lastname: Galateau-Salle
authors.forename: Jean
authors.initials: J
authors.lastname: Feunteun
authors.forename: Jacques
authors.initials: J
authors.lastname: Pouysségur
authors.forename: Stéphane
authors.initials: S
authors.lastname: Richard
authors.forename: Betty
authors.initials: B
authors.lastname: Gardie
mesh_terms: D000328:Adult; D005260:Female; D018095:Germ-Line Mutation; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006720:Homozygote; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D019656:Loss of Heterozygosity; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000235:genetics; D010235:Paraganglioma / Q000235:genetics*; D010375:Pedigree; D011086:Polycythemia / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases