Duplication of theDR3Gene on Human Chromosome 1p36 and Its Deletion in Human Neuroblastoma |
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| Authors: | Jose Grenet Virginia Valentine Jeremy Kitson Haimin Li Stuart N Farrow Vincent J Kidd |
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| Institution: | aDepartment of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38101;bDepartment of Experimental Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38101;cCell Biology Unit, Glaxo-Wellcome Medicines Research Centre, Stevenage, Hertfordshire, SG1 2NY, United Kingdom |
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| Abstract: | The humanDR3gene, whose product is also known as Wsl-1/APO-3/TRAMP/LARD, encodes a tumor necrosis factor-related receptor that is expressed primarily on the surface of thymocytes and lymphocytes. DR3 is capable of inducing both NF-κB activation and apoptosis when overexpressed in mammalian cells, although its ligand has not yet been identified. We report here that theDR3gene locus is tandemly duplicated on human chromosome band 1p36.2–p36.3 and that these genes are hemizygously deleted and/or translocated to another chromosome in neuroblastoma (NB) cell lines with amplifiedMYCN.Duplication of at least a portion of theDR3gene, including the extracellular and transmembrane regions but not the cytoplasmic domain, was demonstrated by both fluorescencein situhybridization and genomic Southern blotting. In most NB cell lines, both theDR3and theDR3Lsequences are simultaneously deleted and/or translocated to another chromosome. Finally, DR3/Wsl-1 protein expression is quite variable among these NB cell lines, with very low or undetectable levels in 7 of 17 NB cell lines. |
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