Vitamin D receptor as a candidate tumor-suppressor gene in severe hyperparathyroidism of uremia Journal Article

  


Authors: Brown, S. B.; Brierley, T. T.; Palanisamy, N.; Salusky, I. B.; Goodman, W.; Brandi, M. L.; Drüeke, T. B.; Sarfati, E.; Ureña, P.; Chaganti, R. S. K.; Pike, J. W.; Arnold, A.
Article Title: Vitamin D receptor as a candidate tumor-suppressor gene in severe hyperparathyroidism of uremia
Abstract: Most chronic renal failure patients with severe refractory hyperparathyroidism harbor at least one monoclonal parathyroid tumor, but the specific acquired genetic defects that confer this clonal selective advantage remain poorly understood. Somatic inactivation of the vitamin D receptor (VDR) gene could contribute to clonal outgrowth, because a parathyroid cell containing this lesion would have an impaired response to the antiproliferative influence of 1,25-dihydroxyvitamin D3. Furthermore, diminished expression of VDR protein has been described in uremia-associated parathyroid tumors. Therefore, to assess VDR gene inactivation's potential pathogenetic role in this disease, we rigorously analyzed the VDR gene in 59 parathyroid tumors surgically resected from uremic patients. First, Southern blotting and/or PCR analyses of 29 tumor samples from 14 genetically informative patients revealed no allelic losses at the VDR locus. Next, direct DNA sequencing of all VDR splice junctions, associated intronic sequences, and virtually the entire VDR-coding region for all 59 tumors revealed no acquired mutations. Last, 37 tumor DNA samples were subjected to comparative genomic hybridization, and no chromosomal losses in the VDR region (12cen-q12) were observed. These observations suggest that inactivating defects within the VDR gene do not commonly contribute to the primary pathogenesis of severe refractory hyperparathyroidism in uremia.
Keywords: adult; controlled study; human tissue; protein expression; middle aged; major clinical study; polymerase chain reaction; gene locus; alleles; calcitriol; tumor suppressor gene; hyperparathyroidism; base sequence; dna sequence; gene inactivation; nucleic acid hybridization; genetic disorder; loss of heterozygosity; vitamin d receptor; parathyroid cell; parathyroid tumor; comparative genomic hybridization; polymorphism, genetic; receptor gene; chronic kidney failure; genes, tumor suppressor; chromosomes; southern blotting; uremia; receptors, calcitriol; hyperparathyroidism, secondary; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Endocrinology and Metabolism
Volume: 85
Issue: 2
ISSN: 0021-972X
Publisher: Oxford University Press  
Date Published: 2000-02-01
Start Page: 868
End Page: 872
Language: English
DOI: 10.1210/jcem.85.2.6426
PUBMED: 10690903
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-17744385121&partnerID=40&md5=3733420ab7bbf492b0761670c7623705
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Nallasivam Palanisamy
    29 Palanisamy
  2. Raju S K Chaganti
    391 Chaganti
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