Genomic instability and loh at 2 polymorphic sites in the h-ras1 gene

Several repetitive elements have been associated with and identified in the surrounding region and within the human c-H-ras1 gene. The polymorphism exhibited by these sites provides valuable information regarding the function and structure of the H-ras gene. We have investigated two such polymorphic sites: i) a hexanucleotide microsatellite region (HRMS) within intron 1 of H-ras and ii) the VTR region at the 3' end of the gene. Comparison between normal and tumor tissues from 25 samples of bladder cancer revealed that 5 samples (20%) exhibited LOH at these polymorphic sites indicating that an allelic loss had occured at the H-ras locus. Furthermore, instability was detected in 4 cases at the hexanucleotide locus, while the VTR region was found unaffected. The two polymorphic sites are in a strong linkage disequilibrium in normal tissues, while in tumor tissues with genomic instability this linkage is altered, possibly leading to differential regulation of the H-ras. Also a previously reported allele at the HRMS locus was found to behave in a manner that preserves the linkage between the two polymorphic sites in normal tissues.