Abnormal c-myc oncogene DNA methylation in human bladder cancer: possible role in tumor progression

It has been suggested that the hypermethylation of normally unmethylated DNA sequences plays a critical role in the genesis and progression of human tumors. Although the molecular bases of this mechanism have not been completely explained, the altered methylation pattern of the c-myc oncogene is supposed to represent an important step in tumor development.

We have analyzed tissue samples from 47 urinary bladder tumors (43 primary transitional and 4 squamous cell carcinomas) and the respective blood with HpaII methyl-sensitive endonuclease digestion and the Southern blotting technique to detect the methylation pattern in a widespread area in and around the c-myc oncogene.

Data presented in this study showed significant differences between 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 compared to normal tissue.

Although the correlation between superficial and infiltrating forms was not statistically significant, we did, however, find differences in aggressive neoplastic behavior. This suggested that local hypermethylation may be considered as one potential mechanism for increasing genetic alterations in bladder cancer formation.