Cloning and characterization of loci surrounding the familial renal cell carcinoma t(3;8) translocation break point
A major goal of gene mapping is to identify candidate oncogenes and tumor suppressor genes, that might play an important role in the pathogenesis of cancer. In the present study we mapped several important genes, using somatic cell hybrid panels and fluorescence in situ hybridization (FISH) methodologies. We further investigated the role of such genes in tumor specific chromosomal translocations. We mapped a novel member of the receptor tyrosine phosphatase gene family, protein tyrosine phosphatase gamma (PTPRG), to the short arm of chromosome 3, region 3p14.2. This chromosome region harbors two important cytogenetic markers: (a) the t(3;8) constitutional translocation breakpoint, associated with familial renal cell carcinoma (RCC), and (b) the most common aphidicolin induced fragile site in the human genome, FRA3B. Because the chromosome location and enzymatic properties of the PTPRG gene suggested a candidate tumor suppressor gene, we undertook a detailed study of the gene structure in normal cells, t(3;8) carrier cells and kidney tumors. We determined that the gene consisted of 30 exons distributed over 780 kb and tested for PTPRG mutations in 28 tumor DNAs from clear cell RCCs and no mutations were detected any tumor specimen. In parallel, we cloned the t(3;8) breakpoint, characterized homozygous deletions in tumor derived cell lines of epithelial origin, that lie within the fragile site, FRA3B. Also, we narrowed a potential tumor suppressor locus to 500 kb flanking the t(3;8) break. This region includes the FRA3B and the transcriptional regulatory region of PTPRG gene.
Kastury, Veera Kumar, "Cloning and characterization of loci surrounding the familial renal cell carcinoma t(3;8) translocation break point" (1996). ETD Collection for Thomas Jefferson University. AAI9633540.