title: Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia.
abstract: Hypoxia-inducible factors are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. When these proteins are dysregulated, they contribute to tumorigenesis and cancer progression. However, mutations in genes encoding α subunits of hypoxia-inducible factors (HIF-α) have not previously been identified in any cancer. Here we report two novel somatic gain-of-function mutations in the gene encoding hypoxia-inducible factor 2α (HIF2A) in two patients, one presenting with paraganglioma and the other with paraganglioma and somatostatinoma, both of whom had polycythemia. The two mutations were associated with increased HIF-2α activity and increased protein half-life.
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Chunzhang
authors.initials: C
authors.lastname: Yang
authors.forename: Felipe
authors.initials: F
authors.lastname: Lorenzo
authors.forename: Maria
authors.initials: M
authors.lastname: Merino
authors.forename: Tito
authors.initials: T
authors.lastname: Fojo
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
authors.forename: Vera
authors.initials: V
authors.lastname: Popovic
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000008:Abdominal Neoplasms / Q000150:complications / Q000235:genetics*; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000235:genetics*; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006900:Hydroxylation; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics; D010235:Paraganglioma / Q000097:blood / Q000150:complications / Q000235:genetics*; D011086:Polycythemia / Q000209:etiology*; D013005:Somatostatinoma / Q000150:complications / Q000235:genetics*; D014158:Transcription, Genetic; D015854:Up-Regulation; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1