Screening for submicroscopic chromosomal rearrangements in Wilms tumor using whole-genome microarrays

Wilms tumor is the fourth most common malignancy of childhood; its pathogenesis, however, remains largely unknown. With advancements in cytogenetic techniques, such as array comparative genomic hybridization (aCGH), there is new hope for uncovering small chromosomal microdeletions or microduplications that may contribute to our understanding of Wilms tumor. We performed aCGH on 10 samples of Wilms tumor with normal conventional cytogenetic and chromosomal CGH findings. Array CGH revealed abnormalities in 3 of the 10 samples, including microdeletions (2q37.1, 7q31∼q32, and 11q22.3), microduplication (18q21.1), and gains and losses of larger chromosomal areas (1q and 7q gain and loss of 7p, 11q, 14q, and 16q). Fluorescence in situ hybridization (FISH) analysis confirmed the abnormalities and revealed the majority of them existed only in a proportion cells (≥30% of cells). We also performed aCGH on three samples of Wilms tumor with previously identified translocations between chromosomes 1 and 16, to determine the breakpoints. The breakpoints were seen in the pericentromeric regions of both chromosomes. Array CGH is useful for identifying submicroscopic changes in Wilms tumor and is more sensitive for detecting clonal abnormalities than conventional methods.