Wilms' tumor with an apparently balanced translocation t(X;18) resulting in deletion of the WTX gene

Abstract

The recent description of a new X chromosome tumor suppressor gene, WTX, that is commonly inactivated in Wilms' tumor prompted us to examine the possible involvement of WTX in a case of Wilms' tumor containing an apparently balanced reciprocal translocation between chromosomes X and 18 (t(X;18)(q11;p11)). Fluorescence in situ hybridization (FISH) analysis of paraffin tumor sections indeed revealed a deletion of the WTX locus at Xq11. High-resolution array comparative genomic hybridization (array CGH) analysis of tumor DNA revealed a 1.5 Mb chromosome deletion encompassing the WTX gene at Xq11. No loss of genetic material was detected on chromosome 18. Interestingly, unlike most tumors with acquired chromosomal translocations, where a new fusion oncogene or promoter-oncogene fusion is created and drives tumor growth, the t(X;18) in this tumor appears to drive tumorigenesis via deletion of a tumor suppressor. This case demonstrates the importance of array CGH and FISH as adjuncts in tumor cytogenetics and in identifying pathogenic microdeletions in "balanced" translocations that are not truly balanced.