An X Chromosome Gene, <i>WTX</i> , Is Commonly Inactivated in Wilms Tumor

Abstract

Wilms tumor is a pediatric kidney cancer associated with inactivation of the WT1 tumor-suppressor gene in 5 to 10% of cases. Using a high-resolution screen for DNA copy-number alterations in Wilms tumor, we identified somatic deletions targeting a previously uncharacterized gene on the X chromosome. This gene, which we call WTX , is inactivated in approximately one-third of Wilms tumors (15 of 51 tumors). Tumors with mutations in WTX lack WT1 mutations, and both genes share a restricted temporal and spatial expression pattern in normal renal precursors. In contrast to biallelic inactivation of autosomal tumor-suppressor genes, WTX is inactivated by a monoallelic “single-hit” event targeting the single X chromosome in tumors from males and the active X chromosome in tumors from females.

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Affiliated Institutions

• Brigham and Women's Hospital US
• Massachusetts General Hospital US
• Harvard University US
• Boston Children's Hospital US
• Johns Hopkins Medicine US
• Johns Hopkins University US
• Memorial Sloan Kettering Cancer Center US

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