Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia.
Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia.
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DOI：
10.1056/nejmoa1205119
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发表时间：
2012-09-06
期刊：
影响因子：
--
通讯作者：
Pacak K
中科院分区：
文献类型：
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作者：
Zhuang Z;Yang C;Lorenzo F;Merino M;Fojo T;Kebebew E;Popovic V;Stratakis CA;Prchal JT;Pacak K
缺氧诱导因子（HIF）是控制能量、铁代谢、红细胞生成和发育的转录因子，并且当失调时，促进肿瘤发生、癌症进展和侵袭。然而，HIFα突变以前没有在任何癌症中被发现。在这里，我们报告了两个新的体细胞功能获得性HIF 2 α突变的两个病人，一个表现为副神经节瘤，第二个表现为副神经节瘤和生长抑素瘤。两种突变均显示增加HIF 2 α活性和蛋白半衰期。虽然已在嗜铬细胞瘤/副神经节瘤中报道了HIFα调节因子（包括VHL和EGLN 1）的种系突变，但这是首次报道HIF中的体细胞功能获得性突变。
Hypoxia inducible factors (HIFs) are transcription factors controlling energy, iron metabolism, erythropoiesis, and development, and, when dysregulated, contribute to tumorigenesis, cancer progression, and invasion. However, HIFα mutations have not previously been identified in any cancer. Here we report two novel somatic gain-of-function HIF2α mutations in two patients, one presenting with a paraganglioma and a second with both paraganglioma and somatostatinoma. Both mutations were shown to confer increased HIF2α activity and protein half-life. While germline mutations of regulators of HIFα, including VHL and EGLN1, have been reported in pheochromocytomas/paragangliomas, this is the first report of a somatic gain-of-function mutation in HIF.