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Second gene linked to familial testicular cancer
Date:6/29/2009

ory, could affect progression of testicular cancer.

In this study, Anelia Horvath, Ph.D., Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), performed the laboratory research and Larissa Korde, M.D., NCI, led the clinical cancer genetics study which identified the multiple-case testicular cancer families used for the DNA analysis. The NICHD and NCI are parts of NIH.

The researchers found that seven different mutations in the gene in question, PDE11A, created abnormal versions of the PDE11A enzyme that slowed down the enzyme's destruction of cyclic AMP.

"The mutations don't cause cancer directly, but instead appear to increase an individual's susceptibility to developing a tumor," explained the study's senior author, Constantine Stratakis, M.D., D.Sc., chief of NICHD's Section on Endocrinology and Genetics. "Almost one out of every five families we studied had a variation in the gene that affected its functioning."

To conduct the research, Stratakis and his colleagues analyzed the portion of the DNA from 95 familial testicular cancer patients that contains the PDE11A gene. They found seven mutations in the cancer patients, and noted that the rate at which they were detected was much higher than that seen in the DNA of people without testicular cancer.

The researchers also had access to the DNA of a group of healthy men, who had been screened for diseases of the endocrine organs, including the testicles. None of the men who screened negative carried any of the genetic mutations identified in the familial testicular cancer patients. "Because this group had no mutations in PDE11A, we were more confident that the mutations had something to do with testicular cancer," said Korde.

Learning how disruptions in the PDE11A enzyme lead to an increased risk of tumor formation may help researchers identify other proteins that also play a role, Stratakis said. He indicated that a good
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Contact: Robert Bock
bockr@mail.nih.gov
301-496-5133
NIH/National Institute of Child Health and Human Development
Source:Eurekalert

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