PHD2 mutation and congenital erythrocytosis with paraganglioma.
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.
Ladroue
Charline
C
Génétique Oncologique, Ecole Pratique des Hautes Etudes and Centre National de la Recherche Scientifique (FRE 2939), Institut de Cancérologie Gustave Roussy, Villejuif, France.
Carcenac
Romain
R
Leporrier
Michel
M
Gad
Sophie
S
Le Hello
Claire
C
Galateau-Salle
Françoise
F
Feunteun
Jean
J
Pouysségur
Jacques
J
Richard
Stéphane
S
Gardie
Betty
B
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
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