The examination of 70 primary transitional cell carcinomas for allelic loss of microsatellite markers spanning chromosome 9 suggests two possible regions for the location of putative tumor suppressor genes. These areas mapped to a region between D9S171 and D9S283 on 9P21-q21-22 and another area telomeric to 9q33. The human growth-arrest-specific gene, GAS1 has been mapped to chromosome 9q21.3-q22 and has been shown to be proximal to marker D9S121. GAS1 has been shown to block cell proliferation in T24 bladder carcinoma cell lines thus indicating its possible role as a tumor suppressor gene in bladder cancer. The role of the tumor suppressing properties of GAS1 in bladder tumor progression from the T0 to the T1 stage was studied using DNA from bladder tumors of 15 patients. Single strand conformational polymorphism (SSCP) analysis was used to determine the status of the GAS1 gene in T0 and T1 tumors. Of the 15 samples, one revealed an aberrant migration shift compared to the pattern observed in the remaining patients. To further analyze the abnormally shifted band, this fragment was cloned and sequenced. Sequence analysis revealed a C→T transition mutation at position 674 of the GAS1 gene. Although this finding corresponds to a silent mutation (Ala→Ala), splice sites must be considered which may affect expresion and gene function. Such a mutation may be important if it results in the loss of the tumor supressing properties of GAS1. This loss of function would allow for the progression of bladder tumors to a more advanced stage.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Jan 1 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)