Affiliations: [a] Department of Clinical Genetics, Medical University of Łódź, Łódź, Poland | [b] Department of Urology, John Paul II Regional Hospital Beƚchatów, Beƚchatów, Poland
Correspondence:
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Corresponding author: Michaƚ Pietrusiński, Department of Clinical Genetics, Medical University of Łódź, 92-213 Łódź, Poland. Te.: +4842 2725357; E-mail:michal.pietrusinski@umed.lodz.pl
Abstract: BACKGROUND: Promoter hypermethylation can be a useful biomarker for
early detection and prognosis of bladder cancer, monitoring response to
treatment and complement classical diagnostic procedures. OBJECTIVE: The molecular test was performed on DNA from bladder
cancer cells in voided urine samples, tumor tissue DNA and normal control
DNAs. We aimed to assess the diagnostic potential of epigenetic changes in
urine DNA from bladder cancer cases at various clinico-pathological stages
of the disease. METHODS: The methylation status of 5 genes (p14ARF, p16INK4A, RASSF1A,
DAPK, APC) in 113 tumor samples paired with voided urine specimens was analyzed by MSP.
We compared the results of methylation analysis with UroVysion test. RESULTS: The methylation profile in tumor/urine DNA was significantly correlated (p ≤ 0,05)
with tumor grade in p14ARF, RASSF1a, APC/p14ARF, APC genes,
respectively and with stage in p14ARF, RASSF1a/p14ARF genes, respectively.
The results of UroVysion test were in correlation with hypermethylation both in tumor and urine DNA
in p14ARF, RASSF1a and APC genes (p = 0,008; 0,02 and 0,04, respectively). CONCLUSIONS: Promoter hypermethylation of tumor suppressor genes is
a frequent mechanism in bladder cancer. We found promoter hypermethylation
in all grades and stages of all cases examined. Methylation profile of
selected suppressor genes may be a potential useful biomarker and enhance
early detection of bladder cancer using a noninvasive urine test.
Keywords: Bladder cancer, DNA methylation, cancer epigenetics
