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Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility

Astuti, D. and Ricketts, C. J. and Chowdhury, R. and McDonough, M. A. and Gentle, D. and Kirby, G. and Schlisio, S. and Kenchappa, R. S. and Carter, B. D. and Kaelin, W. G. and Ratcliffe, P. J. and Schofield, C. J. and Latif, F. and Maher, Eamonn R (2010) Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. Endocrine Related Cancer, 18 (1). p. 73. ISSN 1351-0088

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URL of Published Version: http://dx.doi.org/10.1677/ERC-10-0113

Identification Number/DOI: 10.1677/ERC-10-0113

Germline mutations in the von Hippel–Lindau disease (VHL) and succinate dehydrogenase subunit B (SDHB) genes can cause inherited phaeochromocytoma and/or renal cell carcinoma(RCC). Dysregulation of the hypoxia-inducible factor (HIF) transcription factors has been linked to VHL and SDHB-related RCC; both HIF dysregulation and disordered function of a prolyl hydroxylase domain isoform 3 (PHD3/EGLN3)-related pathway of neuronal apoptosis have been linked to the development of phaeochromocytoma. The 2-oxoglutarate-dependent prolyl hydroxylase enzymes PHD1 (EGLN2), PHD2 (EGLN1) and PHD3 (EGLN3) have a key role in regulating the stability of HIF-a subunits (and hence expression of the HIF-a transcription factors). A germline PHD2 mutation has been reported in association with congenital erythrocytosis and recurrent extra-adrenal phaeochromocytoma. We undertook mutation analysis of PHD1, PHD2 and PHD3 in two cohorts of patients with features of inherited phaeochromocytoma (nZ82) and inherited RCC (nZ64) and no evidence of germline mutations in known susceptibility genes. No confirmed pathogenic mutations were detected suggesting that mutations in these genes are not a frequent cause of inherited phaeochromocytoma or RCC.

Type of Work:Article
Date:2010 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:RC0254 Neoplasms. Tumors. Oncology (including Cancer)
RC Internal medicine
Institution:University of Birmingham
Copyright Holders:Society for Endocrinology
ID Code:559
Refereed:YES
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