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

Rivera, Miguel N.
Kim, Woo Jae
Wells, Julie
Driscoll, David R.
Brannigan, Brian W.
Han, Moonjoo
Kim, James C.
Feinberg, Andrew P.
Gerald, William L.
Vargas, Sara O.
Chin, Lynda
Iafrate, A. John
Bell, Daphne W.
Haber, Daniel A.

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

†To whom correspondence should be addressed. E-mail: [email protected]

Supporting Online Material: www.sciencemag.org/cgi/content/full/1137509/DC1; Materials and Methods; Figs. S1 to S4; Tables S1 to S4; References

13 November 2006; accepted 20 November 2006

Published online 4 January 2007; 10.1126/science.1137509

Include this information when citing this paper.

Science 315(5812):p 642-645, February 2, 2007.

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.