title: An X chromosome gene, WTX, 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.
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical Center, Boston, MA 02114, USA.
authors.forename: Miguel N
authors.initials: MN
authors.lastname: Rivera
authors.forename: Woo Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Julie
authors.initials: J
authors.lastname: Wells
authors.forename: David R
authors.initials: DR
authors.lastname: Driscoll
authors.forename: Brian W
authors.initials: BW
authors.lastname: Brannigan
authors.forename: Moonjoo
authors.initials: M
authors.lastname: Han
authors.forename: James C
authors.initials: JC
authors.lastname: Kim
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
authors.forename: William L
authors.initials: WL
authors.lastname: Gerald
authors.forename: Sara O
authors.initials: SO
authors.lastname: Vargas
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.forename: Daphne W
authors.initials: DW
authors.lastname: Bell
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D016162:Genes, Wilms Tumor; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D009396:Wilms Tumor / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics
chemical_list: C517118:AMER1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D025521:Tumor Suppressor Proteins; D051176:beta Catenin