Ladroue Charline, Carcenac Romain, Leporrier Michel, Gad Sophie, Le Hello Claire, Galateau-Salle Françoise, Feunteun Jean, Pouysségur Jacques, Richard Stéphane, Gardie Betty
Génétique Oncologique, Ecole Pratique des Hautes Etudes and Centre National de la Recherche Scientifique (FRE 2939), Institut de Cancérologie Gustave Roussy, Villejuif, France.
N Engl J Med. 2008 Dec 18;359(25):2685-92. doi: 10.1056/NEJMoa0806277.
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.
脯氨酰羟化酶结构域（PHD）蛋白在调节缺氧诱导因子（HIF）方面发挥着主要作用，HIF可诱导参与血管生成、红细胞生成以及细胞代谢、增殖和存活的基因表达。脯氨酰羟化酶结构域2基因（PHD2）的种系突变已在家族性红细胞增多症患者中被报道，但未发现与肿瘤相关。我们描述了一名患有红细胞增多症和复发性副神经节瘤的患者，该患者携带一种新发现的PHD2突变。这种突变影响PHD2功能并使HIF-α蛋白稳定。此外，我们证明肿瘤中PHD2存在杂合性缺失，提示PHD2可能是一种肿瘤抑制基因。
