Document Detail


Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer.
MedLine Citation:
PMID:  8001233     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The consistent deletion of 3p21 in lung cancer has led to intensive efforts to identify a lung tumor suppressor gene at this locus. We recently mapped the gene for the selenium-dependent drug-detoxifying enzyme glutathione peroxidase 1 (GPX1) to this location by in situ hybridization. We developed a polymerase chain reaction-based assay which demonstrated the existence of three GPX1 alleles characterized by the number of alanines in a polyalanine coding sequence in exon 1. These three alleles produced a heterozygote frequency of 70% in two separate populations: normal tissue DNA taken from Centre d'Etude du Polmorphisme Humain (CEPH) parents and normal tissue taken from cancer patients. In contrast, 10 heterozygote tumors were detected out of 64 lung cancer specimens. Linkage analysis of GPX1 to Genethon 3p markers in CEPH pedigrees demonstrated that GPX1 was located between the two microsatellite markers believed to flank the lung cancer deletion site. Nucleotide sequence analysis of GPX1 alleles did not reveal any mutations of this gene in lung tumors. However, sequence analysis did reveal that the three GPX1 alleles were characterized by three nucleotide substitutions in addition to the polyalanine polymorphism, including a substitution at codon 198 which results in either a proline or leucine at that position. Therefore, the different GPX1 alleles encode structurally different hGPx1 subunits. In addition, analysis of allele frequency suggests that the GPX1*ALA7 allele may occur less frequently in tumors with 3p21 deletions.
Authors:
J A Moscow; L Schmidt; D T Ingram; J Gnarra; B Johnson; K H Cowan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Carcinogenesis     Volume:  15     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1995-01-26     Completed Date:  1995-01-26     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2769-73     Citation Subset:  IM    
Affiliation:
Medicine Branch, National Cancer Institute, Bethesda, MD 20892.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Amino Acid Sequence
Base Sequence
Carcinoma, Non-Small-Cell Lung / enzymology,  genetics*
Chromosomes, Human, Pair 3
Cytosol / enzymology
DNA Mutational Analysis
DNA, Neoplasm / genetics
Gene Frequency
Genes
Genotype
Glutathione Peroxidase / genetics*
Humans
In Situ Hybridization
Lung Neoplasms / enzymology,  genetics*
Molecular Sequence Data
Neoplasm Proteins / genetics*
Polymorphism, Genetic
Reference Values
Selenium / physiology
Sequence Deletion
Chemical
Reg. No./Substance:
0/DNA, Neoplasm; 0/Neoplasm Proteins; 7782-49-2/Selenium; EC 1.11.1.9/Glutathione Peroxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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