Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility.
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;...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1826277659918729216 |
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| author | Astuti, D Ricketts, C Chowdhury, R McDonough, M Gentle, D Kirby, G Schlisio, S Kenchappa, R Carter, B Kaelin, W Ratcliffe, P Schofield, C Latif, F Maher, E |
| author_facet | Astuti, D Ricketts, C Chowdhury, R McDonough, M Gentle, D Kirby, G Schlisio, S Kenchappa, R Carter, B Kaelin, W Ratcliffe, P Schofield, C Latif, F Maher, E |
| author_sort | Astuti, D |
| collection | OXFORD |
| description | 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-α subunits (and hence expression of the HIF-α 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 (n=82) and inherited RCC (n=64) 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. |
| first_indexed | 2024-03-06T23:32:15Z |
| format | Journal article |
| id | oxford-uuid:6c73f375-17f1-4699-b881-6c43f7f4af16 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:32:15Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:6c73f375-17f1-4699-b881-6c43f7f4af162022-03-26T19:10:55ZMutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6c73f375-17f1-4699-b881-6c43f7f4af16EnglishSymplectic Elements at Oxford2011Astuti, DRicketts, CChowdhury, RMcDonough, MGentle, DKirby, GSchlisio, SKenchappa, RCarter, BKaelin, WRatcliffe, PSchofield, CLatif, FMaher, EGermline 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-α subunits (and hence expression of the HIF-α 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 (n=82) and inherited RCC (n=64) 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. |
| spellingShingle | Astuti, D Ricketts, C Chowdhury, R McDonough, M Gentle, D Kirby, G Schlisio, S Kenchappa, R Carter, B Kaelin, W Ratcliffe, P Schofield, C Latif, F Maher, E Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. |
| title | Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. |
| title_full | Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. |
| title_fullStr | Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. |
| title_full_unstemmed | Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. |
| title_short | Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. |
| title_sort | mutation analysis of hif prolyl hydroxylases phd egln in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility |
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