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Novel HIF2A mutations disrupt oxygen sensing, leading to polycythemia, paragangliomas, and somatostatinomas.

ABSTRACT: Hypoxia-inducible factors (HIFs) control the cellular response to hypoxia and, when dysregulated, contribute to tumorigenesis. Previously, we identified 2 gain-of-function somatic mutations in patients presenting with multiple paragangliomas or somatostatinomas, and polycythemia. Here, we report 2 additional unique HIF2A mutations, which disrupt the hydroxylation domain recognized by prolyl hydroxylase domain-2 containing protein, leading to stabilization of HIF-2? and increased expression of hypoxia-related genes.

SUBMITTER: Yang C

PROVIDER: S-EPMC3612863 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Novel HIF2A mutations disrupt oxygen sensing, leading to polycythemia, paragangliomas, and somatostatinomas.

Yang Chunzhang C Sun Michael G MG Matro Joey J Huynh Thanh T TT Rahimpour Shervin S Prchal Josef T JT Lechan Ronald R Lonser Russell R Pacak Karel K Zhuang Zhengping Z

Blood 20130129 13

Hypoxia-inducible factors (HIFs) control the cellular response to hypoxia and, when dysregulated, contribute to tumorigenesis. Previously, we identified 2 gain-of-function somatic mutations in patients presenting with multiple paragangliomas or somatostatinomas, and polycythemia. Here, we report 2 additional unique HIF2A mutations, which disrupt the hydroxylation domain recognized by prolyl hydroxylase domain-2 containing protein, leading to stabilization of HIF-2α and increased expression of hy ...[more]

PMID: 23361906

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