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Published Online January 4, 2007
Science DOI: 10.1126/science.1137509

Reports

Submitted on November 13, 2006
Accepted on December 20, 2006

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

Miguel N. Rivera 1, Woo Jae Kim 2, Julie Wells 2, David R. Driscoll 2, Brian W. Brannigan 2, Moonjoo Han 3, James C. Kim 3, Andrew P. Feinberg 4, William L. Gerald 5, Sara O. Vargas 6, Lynda Chin 7, Anthony John Iafrate 3, Daphne W. Bell 2, Daniel A. Haber 8*

1 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
2 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02115, USA.
3 Department of Pathology, Massachusetts General 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.
8 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02115, USA; Present address: National Human Genome Research Institute, Bethesda, MD 20892, USA.

* To whom correspondence should be addressed.
Daniel A. Haber , E-mail: haber{at}helix.mgh.harvard.edu

Wilms tumor is an embryonal 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 novel 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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