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Originally published in Science Express on 4 January 2007
Science 2 February 2007:
Vol. 315. no. 5812, pp. 642 - 645
DOI: 10.1126/science.1137509
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Reports

An X Chromosome Gene, WTX, Is Commonly Inactivated in Wilms Tumor

Miguel N. Rivera,1,2,3 Woo Jae Kim,1 Julie Wells,1 David R. Driscoll,1 Brian W. Brannigan,1 Moonjoo Han,2 James C. Kim,2 Andrew P. Feinberg,4 William L. Gerald,5 Sara O. Vargas,6 Lynda Chin,7 A. John Iafrate,2 Daphne W. Bell,1* Daniel A. Haber1{dagger}

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.

1 Massachusetts General Hospital Cancer Center, Harvard Medical Center, Boston, MA 02114, USA.
2 Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
3 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
4 Division of Molecular Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
5 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
6 Department of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
7 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

* Present address: National Human Genome Research Institute, Bethesda, MD 20892, USA.

{dagger} To whom correspondence should be addressed. E-mail: haber{at}helix.mgh.harvard.edu

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