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American Association for Cancer Research, Clinical Cancer Research, 24(14), p. 8198-8204, 2008

DOI: 10.1158/1078-0432.ccr-08-1103

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Allelic imbalance analysis using a single-nucleotide polymorphism microarray for the detection of bladder cancer recurrence.

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Abstract Purpose: Non–muscle-invasive bladder cancer is a frequently occurring cancer, with an extremely high recurrence risk. Recurrence detection is based on cytology and urethrocystoscopy. A previous study suggested that a single-nucleotide polymorphism (SNP) array may be effective for noninvasive detection of allelic imbalances in urine. We investigated whether this method is suitable to detect allelic imbalance as an indicator of recurrences in non–muscle-invasive bladder cancer follow-up. Experimental Design: DNA from blood and urine from 158 patients (113 with and 45 without recurrence) was hybridized to the Affymetrix GeneChip Mapping 10K 2.0. Allelic imbalance detection was based on SNPs showing changes from heterozygosity in blood to homozygosity in urine and on automatic analysis of copy number changes using Copy Number Analyser for GeneChip. Results: Urine samples with tumor showed allelic imbalance at 0.4% of all informative SNPs. In samples without tumors, 0.04% of these SNPs were affected (P = 0.07). In addition, Copy Number Analyser for GeneChip analysis showed more copy number changes in samples with a tumor (P = 0.001). Losses and gains of chromosomal regions showed clustering, overlapping with known bladder cancer loci. However, 25 (22%) patients with a tumor recurrence did not display any regions with copy number changes, whereas 24 (53%) individuals without a recurrence did. Receiver operating characteristic curve analysis using the number of SNPs displaying copy number changes from the Copy Number Analyser for GeneChip analysis resulted in an area under the curve of only 0.67 (95% confidence interval, 0.58-0.76). Conclusion: Single-nucleotide polymorphism microarray analysis of allelic imbalance in urine cannot replace urethrocystoscopy and cytology for the detection of recurrences in non–muscle-invasive bladder cancer follow-up.