"Males have only one X chromosome, so for them a single mutation can silence the gene and cause a tumor," Haber explains. "Females have two X chromosomes, but one is inactivated during normal development. We showed that mutations specifically occur on the active X in female Wilms patients, so it takes a single genetic event to inactivate WTX in either males or females. That's in contrast to other tumor suppressor genes, which only can be inactivated by independent mutations affecting both copies of the gene."

The researchers also found that WTX is expressed in cells involved in embryonic kidney development, suggesting that it normally plays a key role in the organ's formation. They are now investigating the gene's normal function and studying its disruption in an animal model.

"The biology that links pediatric cancers to normal organ development is fascinating," says Haber. "Adult kidney cancers arise slowly from the organ's tubules and are highly resistant to current chemotherapy drugs, but pediatric kidney tumors arise in the early stem cells of the kidney's filtering apparatus and are highly responsive to chemotherapy. Following up on these findings should help us better understand this tumor and may lead to a new appreciation of the X chromosome's role in other forms of cancer." Haber is the Laurel Schwartz Professor of Oncology at Harvard Medical School.