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


METHODS
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).


CONCLUSIONS
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.
Coenen
Marieke J H
MJ
Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Ploeg
Martine
M
Schijvenaars
Mascha M V A P
MM
Cornel
Erik B
EB
Karthaus
Herbert F M
HF
Scheffer
Hans
H
Witjes
J Alfred
JA
Franke
Barbara
B
Kiemeney
Lambertus A L M
LA
D022981:Allelic Imbalance / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D001749:Urinary Bladder Neoplasms / Q000235:genetics*