Researchers at the Massachusetts General Hospital (MGH) Cancer Center have discovered a novel gene mutation associated with Wilms tumor, the most common pediatric kidney cancer. The newly identified gene is mutated in about 30 percent of cases of Wilms tumor and is located on the sex-determining X chromosome, which means that a single altered copy would be sufficient for tumor formation. The new gene does not appear linked to inherited forms of the disease.
"This is the first X chromosome gene directly implicated as a tumor suppressor," says Daniel A. Haber, MD, PhD, director of the MGH Cancer Center and senior author of the report, which will appear in the journal Science and is receiving early online release on the Science Express website at http://www.sciencexpress.org. "It has the potential of someday being a useful prognostic marker for Wilms tumor patients, and learning about its normal function could tell us more about both normal kidney development and tumorigenesis."
Also called nephroblastoma, Wilms tumor develops in one out of 10,000 children and is usually treated successfully with surgery and chemotherapy. Mutations in a gene called WT1, first identified in 1990, cause about 5 percent of cases, and a few other genes are associated with rare syndromes that can include Wilms tumor. Those with a family history of the disease have an increased risk of developing the cancer in both kidneys.
Since so few cases of Wilms tumor could be attributed to the identified mutations, the MGH Cancer Center researchers analyzed tumor samples from 82 patients to search for additional genetic abnormalities. Genome screening and sequencing tests showed that nearly 30 percent of the samples had either deletions or mutations in the same area of the X chromosome, indicating a new cancer gene that the researchers have named WTX. In samples from female patients, mutated copies of WTX were found
Contact: Sue McGreevey
Massachusetts General Hospital