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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-12-13
pubmed:abstractText
Promoter hypermethylation is one of the putative mechanisms underlying the inactivation of negative cell-cycle regulators. We examined whether the methylation status of p16(INK4a) and p14(ARF), genes located upstream of the RB and p53 pathway, is a useful biomarker for the staging, clinical outcome, and prognosis of human bladder cancer. Using methylation-specific PCR (MSP), we examined the methylation status of p16(INK4a) and p14(ARF) in 64 samples from 45 bladder cancer patients (34 males, 11 females). In 19 patients with recurrent bladder cancer, we examined paired tissue samples from their primary and recurrent tumors. The methylation status of representative samples was confirmed by bisulfite DNA sequencing analysis. The median follow-up duration was 34.3 months (range 27.0-100.1 months). The methylation rate for p16(INK4a) and p14(ARF) was 17.8% and 31.1%, respectively, in the 45 patients. The incidence of p16(INKa) and p14(ARF) methylation was significantly higher in patients with invasive (>or=pT2) than superficial bladder cancer (pT1) (p=0.006 and p=0.001, respectively). No MSP bands for p16(INK4a) and p14(ARF) were detected in the 8 patients with superficial, non-recurrent tumors. In 19 patients with tumor recurrence, the p16(INK4a) and p14(ARF) methylation status of the primary and recurrent tumors was similar. Of the 22 patients who had undergone cystectomy, 8 (36.4%) manifested p16(INKa) methylation; p16(INK4a) was not methylated in 23 patients without cystectomy (p=0.002). Kaplan-Meier analysis revealed that patients with p14(ARF) methylation had a significantly poorer prognosis than those without (p=0.029). This is the first study indicating that MSP analysis of p16(INK4a) and p14(ARF) genes is a useful biomarker for the pathological stage, clinical outcome, and prognosis of patients with bladder cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
339
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
790-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16316628-Aged, pubmed-meshheading:16316628-Aged, 80 and over, pubmed-meshheading:16316628-Cyclin-Dependent Kinase Inhibitor p16, pubmed-meshheading:16316628-DNA, Neoplasm, pubmed-meshheading:16316628-DNA Methylation, pubmed-meshheading:16316628-DNA Mutational Analysis, pubmed-meshheading:16316628-Feasibility Studies, pubmed-meshheading:16316628-Female, pubmed-meshheading:16316628-Genetic Testing, pubmed-meshheading:16316628-Humans, pubmed-meshheading:16316628-Male, pubmed-meshheading:16316628-Middle Aged, pubmed-meshheading:16316628-Promoter Regions, Genetic, pubmed-meshheading:16316628-Reproducibility of Results, pubmed-meshheading:16316628-Sensitivity and Specificity, pubmed-meshheading:16316628-Tumor Markers, Biological, pubmed-meshheading:16316628-Tumor Suppressor Protein p14ARF, pubmed-meshheading:16316628-Urinary Bladder Neoplasms
pubmed:year
2006
pubmed:articleTitle
p16INK4a and p14ARF methylation as a potential biomarker for human bladder cancer.
pubmed:affiliation
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-08520, Japan.
pubmed:publicationType
Journal Article, Clinical Trial