| 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. |
| Keywords: |
adult; clinical article; controlled study; human tissue; gene mutation; human cell; gene deletion; mutation; cancer risk; nonhuman; chromosome; mouse; animals; mice; animal tissue; gene; in situ hybridization, fluorescence; gene expression; cell line; alleles; heterozygote; mice, inbred c57bl; kidney neoplasms; childhood cancer; tumor suppressor gene; fluorescence in situ hybridization; kidney; amino acid sequence; molecular sequence data; tumor suppressor proteins; newborn; x chromosome; chromosomes, human, x; x chromosome inactivation; familial cancer; gene inactivation; gene silencing; wt1 protein; kidney cancer; tumor; point mutation; chromosome deletion; beta catenin; comparative genomic hybridization; genomic dna; complementary dna; nephroblastoma; wilms tumor; endocrine system disorder; wtx gene; x chromosome linkage; genes, wilms tumor
|
