An X chromosome gene, WTX, is commonly inactivated in Wilms tumor.
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.
Rivera
Miguel N
MN
Massachusetts General Hospital Cancer Center, Harvard Medical Center, Boston, MA 02114, USA.
Kim
Woo Jae
WJ
Wells
Julie
J
Driscoll
David R
DR
Brannigan
Brian W
BW
Han
Moonjoo
M
Kim
James C
JC
Feinberg
Andrew P
AP
Gerald
William L
WL
Vargas
Sara O
SO
Chin
Lynda
L
Iafrate
A John
AJ
Bell
Daphne W
DW
Haber
Daniel A
DA
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
C517118:AMER1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D025521:Tumor Suppressor Proteins; D051176:beta Catenin