STRUCTURE OF THE HUMAN RECEPTOR TYROSINE PHOSPHATASE GAMMA-GENE (PTPRG) AND RELATION TO THE FAMILIAL RCC T(3-8) CHROMOSOME-TRANSLOCATION

The receptor protein tyrosine phosphatase gamma gene, PTP gamma (locus name PTPRG), was previously mapped to chromosome region 3p14.2, withi n a 2- to 4-Mb region centromeric to the 3p14.2 breakpoint of the t(3; 8) familial renal cell carcinoma (RCC)-associated constitutional chrom osome translocation. Because of its chromosomal position, its enzymati c properties as a receptor phosphatase, which might oppose a growth ac tivating kinase activity, its homozygous deletion in murine L cells, a nd its transcriptional activity in numerous normal tissues, including kidney, the PTP gamma gene was an attractive tumor suppressor gene can didate for renal cell carcinoma. To determine whether the PTP gamma ge ne was a target of loss of heterozygosity or mutation in RCCs and to d etermine its map position relative to the t(3;8) break at 3p14.2, we h ave isolated YAC and lambda genomic clones for the PTP gamma y gene an d other 3p14.2 markers and determined the relative positions of the t( 3;8) break, a 3p14.2 de novo break possibly in a fragile site, and the 5' end of the PTP gamma gene. Additionally, the genomic structure, po sition of the proximal promotor, and intron-exon border sequences of t he 30-exon similar to 780-kb PTP gamma gene have been determined, whic h will facilitate analysis of the PTP gamma gene in tumors. (C) 1996 A cademic Press, Inc.