Duplication of the DR3 gene on human chromosome 1p36 and its deletion in human neuroblastoma.
The human DR3 gene, 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-kappa B activation and apoptosis when overexpressed in mammalian cells, although its ligand has not yet been identified. We report here that the DR3 gene 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 amplified MYCN. Duplication of at least a portion of the DR3 gene, including the extracellular and transmembrane regions but not the cytoplasmic domain, was demonstrated by both fluorescence in situ hybridization and genomic Southern blotting. In most NB cell lines, both the DR3 and the DR3L sequences 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.
Grenet
J
J
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.
Valentine
V
V
Kitson
J
J
Li
H
H
Farrow
S N
SN
Kidd
V J
VJ
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D017353:Gene Deletion; D015698:Genomic Library; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008214:Lymphocytes / Q000378:metabolism; D008322:Mammals; D005810:Multigene Family; D016328:NF-kappa B / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics*; D053219:Receptors, Tumor Necrosis Factor, Member 25; D011994:Recombinant Proteins / Q000096:biosynthesis; D013950:Thymus Gland / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; D011994:Recombinant Proteins; C506033:TNFRSF25 protein, human