Correlations between Histological and Array Comparative Genomic Hybridization Characterizations of Wilms Tumor

Wilms tumor, or nephroblastoma, is the most common pediatric renal malignancy. Its diagnosis is principally based on histology. Several genetic loci have been shown to be associated with Wilms tumor formation, including WT1, WT2, FWT1, FWT2, CTNNB1, WTX, and TP53. Other loci, such as 1p, 2q, 7p, 9q, 12q, 14q, 16q, 17p, and 22, have also been implicated in the etiology of Wilms tumor. The aim of this study is to elucidate the molecular pathogenesis of this tumor. In the present study, we analyzed the histological appearance and copy number aberrations using array comparative genomic hybridization of six Wilms tumors without somatic mutation in the WT1 gene. Many chromosomal aberrations on array comparative genomic hybridization analysis revealed that the genetics of Wilms tumors are extremely complex. Amplifications and deletions of large DNA fragments were observed in some samples. Amplifications of NDUFV1, ZIC2, SIX1, NR2F2, MIR1469, SOX9, JAG1, MIR6870, and GNAS were found in all six Wilms tumors. Moreover, amplifications of five genes were identified in the Wilms tumors of stromal type and amplifications of at least 10 genes were identified in the Wilms tumors of epithelial type. Our results indicated that amplifications of nine genes are the essential events in the tumorigenesis of Wilms tumor, which may inform its clinical and therapeutic management. In addition, mixed type Wilms tumor may be the heterogeneous group able to be classified using genetic results of epithelial and stromal components based on immunohistochemistry.