DUPLICATION OF THE DR3 GENE ON HUMAN-CHROMOSOME 1P36 AND ITS DELETIONIN HUMAN NEUROBLASTOMA

The human DR3 gene, whose product is also known as Wsl-1/APO-3/TRAMP/L ARD, encodes a tumor necrosis factor-related receptor that is expresse d primarily on the surface of thymocytes and lymphocytes. DR3 is capab le of inducing both NF-kappa B activation and apoptosis when overexpre ssed in mammalian cells, although its ligand has not yet been identifi ed. We report here that the DR3 gene locus is tandemly duplicated on h uman chromosome band 1p36.2-p36.3 and that these genes are hemizygousl y 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 NE 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 NE cell lines, with very low or undetectable levels in 7 of 17 NE cell lines. (C) 1998 Academic Pre ss.