PHYSICAL MAPPING AND GENOMIC STRUCTURE OF THE HUMAN TNFR2 GENE

The tumor necrosis factor receptor 2 (TNFR2) gene localizes to 1p36.2, a genomic region characteristically deleted in neuroblastomas and oth er malignancies. In addition, TNFR2 is the principal mediator of the e ffects of TNF on cellular immunity, and it may cooperate with TNFR1 in the killing of nonlymphoid cells. Therefore, we undertook an analysis of the genomic structure and precise physical mapping of this gene. T he TNFR2 gene is contained on 10 exons that span 26 kb. Most of the fu nctional domains of TNFR2 are encoded by separate exons, and each of t he repeats of the extracellular cysteine-rich domain is interrupted by an intron. The genomic structure reveals a close relationship to TNFR 1, another member of the TNFR superfamily. Based on electrophoretic an alysis of yeast artificial chromosomes, TNFR2 maps within 400 kb of th e genetic marker D1S434. In addition, we have identified a new polymor phic dinucleotide repeat within intron 4 of TNFR2. The genetic sequenc e information and exon-intron boundaries we have determined will facil itate mutational analysis of this gene to determine its potential role in neuroblastoma, as well as in other cancers with characteristic del etions or rearrangements of 1p36. (C) 1996 Academic Press, Inc.