ABNORMAL C-MYC ONCOGENE DNA METHYLATION IN HUMAN BLADDER-CANCER - POSSIBLE ROLE IN TUMOR PROGRESSION

Objective: It has been suggested that the hypermethylation of normally unmethylated DNA sequences plays a critical role in the genesis and p rogression of human tumors. Although the molecular bases of this mecha nism have not been completely explained, the altered methylation patte rn of the c-myc oncogene is supposed to represent an important step in tumor development. Methods: We have analyzed tissue samples from 47 u rinary bladder tumors (43 primary transitional and 4 squamous cell car cinomas) and the respective blood with HpaII methyl-sensitive endonucl ease digestion and the Southern blotting technique to detect the methy lation pattern in a widespread area in and around the c-myc oncogene, Results: Data presented in this study showed significant differences b etween the c-myc methylation pattern and pathological grade (p < 0.05) . On the other hand, we did not find a significant correlation between the c-myc methylation pattern and clinical stage. However, a variable covalent alteration of c-myc DNA existed in bladder cancer as compare d to normal tissue. Conclusion: Although the con-elation between super ficial and infiltrating forms was not statistically significant, we di d, however, find differences in aggressive neoplastic behavior. This s uggested that local hypermethylation may be considered as one potentia l mechanism for increasing genetic alterations in bladder cancer forma tion.