Promoter hypermethylation in tumour suppressor genes shows association with stage, grade and invasiveness of bladder cancer.
OBJECTIVE
Superficial bladder cancer is a highly recurrent disease, with progression to muscle invasiveness occurring in 15-30% of cases. Promoter hypermethylation in a panel of tumour suppressor genes involved in cell cycle control, apoptosis and DNA repair was analyzed in superficial bladder tumours in order to evaluate the suitability of epigenetic biomarkers for an earlier prediction of the aggressive course of the disease.


METHODS
Promoter hypermethylation in p16, RARbeta, RASSF1A, DAPK, and MGMT genes was analyzed in 58 cases with superficial bladder cancer and 2 cases with benign urological disease using methylation-specific PCR.


RESULTS
Promoter hypermethylation was frequently detected in RARbeta, RASSF1A and DAPK genes, and 62% of bladder tumours exhibited hypermethylation in at least one gene. The overall frequency of hypermethylation and the number of genes involved increased with tumour stage, grade and muscle invasiveness. Aberrant methylation of RASSF1A and RARbetawas predominant (p < 0.05) in muscle-invasive tumours and high-grade tumours, respectively. Cases with concurrent hypermethylation in DAPK, p16 and RARbeta genes were moresusceptible to relapse.


CONCLUSIONS
The results suggest analysis of promoter hypermethylation as a valuable biomarker for prognosis of the aggressive course of disease in bladder cancer.
Jarmalaite
Sonata
S
Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania. sonata.jarmalaite@gf.vu.lt
Jankevicius
Feliksas
F
Kurgonaite
Kristina
K
Suziedelis
Kestutis
K
Mutanen
Pertti
P
Husgafvel-Pursiainen
Kirsti
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
D004273:DNA, Neoplasm