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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2002-5-2
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pubmed:abstractText |
The von Hippel-Lindau (VHL) tumor suppressor gene targets hypoxia-inducible transcription factors (HIFs) for proteasomal degradation. Erythrocytosis due to inappropriate production of erythropoietin (EPO), one of the HIF target genes, is a classic albeit rare finding in patients with renal cancer. We report the clinical to molecular analysis in a patient in whom a thrombotic myocardial infarction was the first manifestation of a clear cell renal carcinoma associated with an elevated serum EPO level (109 U/L) and erythrocytosis (hemoglobin 200 g/L [20 g/dL]). The tumor strongly expressed EPO messenger RNA and the 2 regulatory subunits HIF-1alpha and HIF-2alpha. Sequence analysis of tumor tissue identified a point mutation of the VHL gene (nucleotide 701 T > C) with a predicted amino acid exchange (Leu163Pro). This structural change, although located at distance to the HIF-binding region, was found to inhibit binding of HIF-1alpha to VHL, thus leading to accumulation of HIF, which drives EPO production.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/VHL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Von Hippel-Lindau Tumor Suppressor...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
99
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3562-5
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11986208-Carcinoma, Renal Cell,
pubmed-meshheading:11986208-Erythropoietin,
pubmed-meshheading:11986208-Genes, Tumor Suppressor,
pubmed-meshheading:11986208-Humans,
pubmed-meshheading:11986208-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:11986208-Kidney Neoplasms,
pubmed-meshheading:11986208-Ligases,
pubmed-meshheading:11986208-Male,
pubmed-meshheading:11986208-Middle Aged,
pubmed-meshheading:11986208-Myocardial Infarction,
pubmed-meshheading:11986208-Point Mutation,
pubmed-meshheading:11986208-Polycythemia,
pubmed-meshheading:11986208-RNA, Messenger,
pubmed-meshheading:11986208-Tomography, X-Ray Computed,
pubmed-meshheading:11986208-Transcription Factors,
pubmed-meshheading:11986208-Tumor Cells, Cultured,
pubmed-meshheading:11986208-Tumor Suppressor Proteins,
pubmed-meshheading:11986208-Ubiquitin-Protein Ligases,
pubmed-meshheading:11986208-Von Hippel-Lindau Tumor Suppressor Protein
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pubmed:year |
2002
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pubmed:articleTitle |
Paraneoplastic erythrocytosis associated with an inactivating point mutation of the von Hippel-Lindau gene in a renal cell carcinoma.
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pubmed:affiliation |
Department of Nephrology and Medical Intensive Care, Charité, Humboldt-University, Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
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