I. Sardi et al., ABNORMAL C-MYC ONCOGENE DNA METHYLATION IN HUMAN BLADDER-CANCER - POSSIBLE ROLE IN TUMOR PROGRESSION, European urology, 31(2), 1997, pp. 224-230
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.