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 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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sardi
I
I
First Medical Clinics, University of Florence, Italy.
Dal Canto
M
M
Bartoletti
R
R
Montali
E
E
D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis*; D003720:Densitometry; D019003:Deoxyribonuclease HpaII / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D004273:DNA, Neoplasm; D019003:Deoxyribonuclease HpaII