Combined cytogenetic and array-based comparative genomic hybridization analyses of Wilms tumors: amplification and overexpression of the multidrug resistance associated protein 1 gene (MRP1) in a metachronous tumor.

Overview

Tumor samples from a variety of Wilms tumors (WT) obtained from three patients were analyzed by cytogenetic and array-based comparative genomic hybridization (CGH) methods. The tumors represented different stages of tumorigenesis and included a unilateral primary WT and contralateral nephrogenic rest (case 1), a primary WT and a contralateral metachronous WT (case 2), and a recurrent WT with lung metastases (case 3). All six specimens exhibited abnormal karyotypes characteristic of different WT levels of progression. Array-based CGH examinations of 57 genes that are commonly amplified in various cancers revealed a 2.6-fold genomic amplification of the multidrug resistance-associated protein 1 (MRP1) gene in the metachronous WT, but no amplification in the primary tumor. This sole amplification event in our series was also confirmed by Southern blot analysis. Furthermore, quantitative reverse transcriptase polymerase chain reaction showed a sixfold overexpression of the MRP1 gene in this metachronous WT relative to the primary tumor. Our findings suggest that for most of the genes examined in this series genomic amplification does not play a role in WT pathogenesis. Isolated amplification and overexpression of the MRP1 gene in the metachronous WT, however, suggest that this gene may be an important factor in the development and progression of metachronous tumors.