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: Zhengping Zhuang, Chunzhang Yang, Felipe Lorenzo, Maria Merino, Tito Fojo, Electron Kebebew, Vera Popovic, Constantine A Stratakis, Josef T Prchal, Karel Pacak
• Journal: The New England journal of medicine (N Engl J Med) Vol. 367 Issue 10 Pg. 922-30 (Sep 06 2012) ISSN: 1533-4406 [Electronic] United States
• PMID: 22931260 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• endothelial PAS domain-containing protein 1

Topics

• Abdominal Neoplasms (complications, genetics)
• Adolescent
• Adrenal Gland Neoplasms (complications, genetics)
• Adult
• Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
• DNA Mutational Analysis
• Female
• Humans
• Hydroxylation
• Mutation
• Pancreatic Neoplasms (genetics)
• Paraganglioma (blood, complications, genetics)
• Polycythemia (etiology)
• Somatostatinoma (complications, genetics)
• Transcription, Genetic
• Up-Regulation