No evidence for large-scale germline genomic aberrations in hereditary bladder cancer patients with high-resolution array-based comparative genomic hybridization.

Linkage studies in high-risk families have led to the identification of several important susceptibility genes for hereditary cancer. Unfortunately, such studies offer limited possibilities in the search for high-penetrance bladder cancer genes, as extended bladder cancer families are very rare. Traditional karyotyping or conventional comparative genomic hybridization (CGH) may reveal constitutional chromosomal anomalies that point to the location of susceptibility genes (1). Both these techniques, however, are hampered by their limited resolution (f3 Mb with CGH). The recent development of array-based CGH has increased this resolution to f100 kb. Using a 32,447 bacterial artificial chromosome array with close to complete coverage of the entire human genome (2, 3), we recently identified several novel submicroscopic interstitial chromosomal abnormalities in patients with unexplained mental retardation (4). In this study, we have used these tiling resolution genomic microarrays to investigate the presence of copy number abnormalities in 10 patients, representing 10 nonrelated Dutch bladder cancer families.