| Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer. | |
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MedLine Citation:
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PMID: 8001233 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J A Moscow; L Schmidt; D T Ingram; J Gnarra; B Johnson; K H Cowan |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Carcinogenesis Volume: 15 ISSN: 0143-3334 ISO Abbreviation: Carcinogenesis Publication Date: 1994 Dec |
Date Detail:
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Created Date: 1995-01-26 Completed Date: 1995-01-26 Revised Date: 2005-11-17 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 2769-73 Citation Subset: IM |
Affiliation:
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Medicine Branch, National Cancer Institute, Bethesda, MD 20892. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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