Coenen Marieke J H, Ploeg Martine, Schijvenaars Mascha M V A P, Cornel Erik B, Karthaus Herbert F M, Scheffer Hans, Witjes J Alfred, Franke Barbara, Kiemeney Lambertus A L M
Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Clin Cancer Res. 2008 Dec 15;14(24):8198-204. doi: 10.1158/1078-0432.CCR-08-1103.
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.
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.
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).
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.
非肌层浸润性膀胱癌是一种常见癌症，复发风险极高。复发检测基于细胞学检查和尿道膀胱镜检查。先前的一项研究表明，单核苷酸多态性（SNP）阵列可能对尿液中等位基因失衡的无创检测有效。我们研究了该方法是否适合作为非肌层浸润性膀胱癌随访中复发指标来检测等位基因失衡。
将158例患者（113例复发患者和45例未复发患者）的血液和尿液中的DNA与Affymetrix GeneChip Mapping 10K 2.0进行杂交。等位基因失衡检测基于从血液中的杂合性变为尿液中的纯合性的SNP，以及使用基因芯片拷贝数分析仪对拷贝数变化进行自动分析。
肿瘤尿液样本中，在所有信息性SNP中0.4%显示等位基因失衡。在无肿瘤样本中，这些SNP的0.04%受到影响（P = 0.07）。此外，基因芯片拷贝数分析仪分析显示肿瘤样本中的拷贝数变化更多（P = 0.001）。染色体区域的缺失和增加呈现聚类，与已知膀胱癌基因座重叠。然而，25例（22%）肿瘤复发患者未显示任何拷贝数变化区域，而24例（53%）未复发个体显示有拷贝数变化区域。使用基因芯片拷贝数分析仪分析中显示拷贝数变化的SNP数量进行的受试者工作特征曲线分析，曲线下面积仅为0.67（95%置信区间，0.58 - 0.76）。
尿液中等位基因失衡的单核苷酸多态性微阵列分析不能替代尿道膀胱镜检查和细胞学检查用于非肌层浸润性膀胱癌随访中的复发检测。
